Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

MicroRNAs in kidney injury and disease

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by degrading or repressing the translation of their target messenger RNAs. As miRNAs are critical regulators of cellular homeostasis, their dysregulation is a crucial component of cell and organ injury. A substantial body of evidence indicates that miRNAs are involved in the pathophysiology of acute kidney injury (AKI), chronic kidney disease and allograft damage. Different subsets of miRNAs are dysregulated during AKI, chronic kidney disease and allograft rejection, which could reflect differences in the physiopathology of these conditions. miRNAs that have been investigated in AKI include miR-21, which has an anti-apoptotic role, and miR-214 and miR-668, which regulate mitochondrial dynamics. Various miRNAs are downregulated in diabetic kidney disease, including the miR-30 family and miR-146a, which protect against inflammation and fibrosis. Other miRNAs such as miR-193 and miR-92a induce podocyte dedifferentiation in glomerulonephritis. In transplantation, miRNAs have been implicated in allograft rejection and injury. Further work is needed to identify and validate miRNAs as biomarkers of graft function and of kidney disease development and progression. Use of combinations of miRNAs together with other molecular markers could potentially improve diagnostic or predictive power and facilitate clinical translation. In addition, targeting specific miRNAs at different stages of disease could be a promising therapeutic strategy.

Key points

  • Dysregulation of microRNAs (miRNAs) has been described in acute kidney injury (AKI), chronic kidney disease (CKD) and alloimmune injury in solid organ transplantation; this dysregulation could contribute to the pathophysiology of these diseases.

  • In AKI, miRNAs have both protective and deleterious effects and might contribute to regulation of cell proliferation, inflammation and apoptotic and fibrotic pathways in tubular epithelial cells and the tubulointerstitial compartment.

  • miRNAs have been implicated in fibrosis in diabetic kidney disease, in the control of cell proliferation and inflammation in glomerulonephritis and in the regulation of tubular cell proliferation and apoptosis in autosomal-dominant polycystic kidney disease.

  • In transplantation, miRNAs have been implicated in rejection and graft injury and could potentially be utilized as biomarkers for surveillance of graft function.

  • Further work is needed to identify and validate miRNAs as biomarkers of kidney disease development and progression.

  • Improved understanding of the mechanisms that underlie miRNA functions in kidney disease is required to identify potential miRNA therapeutic targets to prevent the development or slow the progression of AKI and CKD.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: miRNA biogenesis and action.
Fig. 2: miRNAs in acute kidney injury.
Fig. 3: miRNAs in diabetic kidney disease.
Fig. 4: miRNAs with roles in both AKI and CKD.

Similar content being viewed by others

References

  1. Lee, R. C., Feinbaum, R. L. & Ambros, V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843–854 (1993).

    Article  CAS  PubMed  Google Scholar 

  2. Kozomara, A., Birgaoanu, M. & Griffiths-Jones, S. miRBase: from microRNA sequences to function. Nucleic Acids Res. 47, D155–D162 (2019).

    Article  CAS  PubMed  Google Scholar 

  3. Sun, Y. et al. Development of a micro-array to detect human and mouse microRNAs and characterization of expression in human organs. Nucleic Acids Res. 32, e188 (2004).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Naraba, H. & Iwai, N. Assessment of the microRNA system in salt-sensitive hypertension. Hypertens. Res. 28, 819–826 (2005).

    Article  CAS  PubMed  Google Scholar 

  5. Harvey, S. J. et al. Podocyte-specific deletion of dicer alters cytoskeletal dynamics and causes glomerular disease. J. Am. Soc. Nephrol. 19, 2150–2158 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ho, J. et al. Podocyte-specific loss of functional microRNAs leads to rapid glomerular and tubular injury. J. Am. Soc. Nephrol. 19, 2069–2075 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Shi, S. et al. Podocyte-selective deletion of dicer induces proteinuria and glomerulosclerosis. J. Am. Soc. Nephrol. 19, 2159–2169 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kato, M. et al. MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors. Proc. Natl Acad. Sci. USA 104, 3432–3437 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Wang, Q. et al. MicroRNA-377 is up-regulated and can lead to increased fibronectin production in diabetic nephropathy. FASEB J. 22, 4126–4135 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Pavkovic, M. & Vaidya, V. S. MicroRNAs and drug-induced kidney injury. Pharmacol. Ther. 163, 48–57 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Keller, A. et al. miRNATissueAtlas2: an update to the human miRNA tissue atlas. Nucleic Acids Res. https://doi.org/10.1093/nar/gkab808 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Rose, S. A. et al. A microRNA expression and regulatory element activity atlas of the mouse immune system. Nat. Immunol. 22, 914–927 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Huang, Z. et al. HMDD v3.0: a database for experimentally supported human microRNA-disease associations. Nucleic Acids Res. 47, D1013–D1017 (2019).

    Article  CAS  PubMed  Google Scholar 

  14. Castaño, I. M. et al. microRNA modulation. in Cell Engineering and Regeneration (eds Gimble, J. M., Marolt, D., Oreffo, R., Redl, H. & Wolbank, S.) 1–66 (Springer International Publishing, 2019).

  15. Kim, Y.-K. & Kim, V. N. Processing of intronic microRNAs. EMBO J. 26, 775–783 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. The FANTOM Consortium. et al. An integrated expression atlas of miRNAs and their promoters in human and mouse. Nat. Biotechnol. 35, 872–878 (2017).

    Article  PubMed Central  CAS  Google Scholar 

  17. Lee, Y. et al. MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 23, 4051–4060 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Denli, A. M., Tops, B. B. J., Plasterk, R. H. A., Ketting, R. F. & Hannon, G. J. Processing of primary microRNAs by the microprocessor complex. Nature 432, 231–235 (2004).

    Article  CAS  PubMed  Google Scholar 

  19. Gregory, R. I. et al. The microprocessor complex mediates the genesis of microRNAs. Nature 432, 235–240 (2004).

    Article  CAS  PubMed  Google Scholar 

  20. Lee, Y. et al. The nuclear RNase III Drosha initiates microRNA processing. Nature 425, 415–419 (2003).

    Article  CAS  PubMed  Google Scholar 

  21. Han, J. et al. The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev. 18, 3016–3027 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Fang, W. & Bartel, D. P. MicroRNA clustering assists processing of suboptimal microRNA hairpins through the action of the ERH protein. Mol. Cell 78, 289–302.e6 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bohnsack, M. T., Czaplinski, K. & Gorlich, D. Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA 10, 185–191 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lund, E., Güttinger, S., Calado, A., Dahlberg, J. E. & Kutay, U. Nuclear export of microRNA precursors. Science 303, 95–98 (2004).

    Article  CAS  PubMed  Google Scholar 

  25. Yi, R., Qin, Y., Macara, I. G. & Cullen, B. R. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev. 17, 3011–3016 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Chendrimada, T. P. et al. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature 436, 740–744 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Wilson, R. C. et al. Dicer-TRBP complex formation ensures accurate mammalian microRNA biogenesis. Mol. Cell 57, 397–407 (2015).

    Article  CAS  PubMed  Google Scholar 

  28. Bernstein, E., Caudy, A. A., Hammond, S. M. & Hannon, G. J. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409, 363–366 (2001).

    Article  CAS  PubMed  Google Scholar 

  29. Grishok, A. et al. Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell 106, 23–34 (2001).

    Article  CAS  PubMed  Google Scholar 

  30. Hutvágner, G. et al. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science 293, 834–838 (2001).

    Article  PubMed  Google Scholar 

  31. Hammond, S. M., Boettcher, S., Caudy, A. A., Kobayashi, R. & Hannon, G. J. Argonaute2, a link between genetic and biochemical analyses of RNAi. Science 293, 1146–1150 (2001).

    Article  CAS  PubMed  Google Scholar 

  32. Mourelatos, Z. et al. miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs. Genes Dev. 16, 720–728 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Tabara, H. et al. The rde-1 gene, RNA interference, and transposon silencing in C. elegans. Cell 99, 123–132 (1999).

    Article  CAS  PubMed  Google Scholar 

  34. Treiber, T., Treiber, N. & Meister, G. Regulation of microRNA biogenesis and its crosstalk with other cellular pathways. Nat. Rev. Mol. Cell Biol. 20, 5–20 (2019).

    Article  CAS  PubMed  Google Scholar 

  35. Ha, M. & Kim, V. N. Regulation of microRNA biogenesis. Nat. Rev. Mol. Cell Biol. 15, 509–524 (2014).

    Article  CAS  PubMed  Google Scholar 

  36. Eisen, T. J., Eichhorn, S. W., Subtelny, A. O. & Bartel, D. P. MicroRNAs cause accelerated decay of short-tailed target mRNAs. Mol. Cell 77, 775–785.e8 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Golden, R. J. et al. An argonaute phosphorylation cycle promotes microRNA-mediated silencing. Nature 542, 197–202 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Selbach, M. et al. Widespread changes in protein synthesis induced by microRNAs. Nature 455, 58–63 (2008).

    Article  CAS  PubMed  Google Scholar 

  39. Briskin, D., Wang, P. Y. & Bartel, D. P. The biochemical basis for the cooperative action of microRNAs. Proc. Natl Acad. Sci. USA 117, 17764–17774 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Landgraf, P. et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129, 1401–1414 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Ambros, V. The functions of animal microRNAs. Nature 431, 350–355 (2004).

    Article  CAS  PubMed  Google Scholar 

  42. Guo, Z. et al. Genome-wide survey of tissue-specific microRNA and transcription factor regulatory networks in 12 tissues. Sci. Rep. 4, 5150 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Ameres, S. L. et al. Target RNA-directed trimming and tailing of small silencing RNAs. Science 328, 1534–1539 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. de la Mata, M. et al. Potent degradation of neuronal miRNAs induced by highly complementary targets. EMBO Rep. 16, 500–511 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Bitetti, A. et al. MicroRNA degradation by a conserved target RNA regulates animal behavior. Nat. Struct. Mol. Biol. 25, 244–251 (2018).

    Article  CAS  PubMed  Google Scholar 

  46. Ghini, F. et al. Endogenous transcripts control miRNA levels and activity in mammalian cells by target-directed miRNA degradation. Nat. Commun. 9, 3119 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Shi, C. Y. et al. The ZSWIM8 ubiquitin ligase mediates target-directed microRNA degradation. Science 370, eabc9359 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Han, J. et al. A ubiquitin ligase mediates target-directed microRNA decay independently of tailing and trimming. Science 370, eabc9546 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kingston, E. R. & Bartel, D. P. Global analyses of the dynamics of mammalian microRNA metabolism. Genome Res. 29, 1777–1790 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Wei, Q. et al. Targeted deletion of Dicer from proximal tubules protects against renal ischemia-reperfusion injury. J. Am. Soc. Nephrol. 21, 756–761 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Brandenburger, T., Salgado Somoza, A., Devaux, Y. & Lorenzen, J. M. Noncoding RNAs in acute kidney injury. Kidney Int. 94, 870–881 (2018).

    Article  CAS  PubMed  Google Scholar 

  52. Guo, C., Dong, G., Liang, X. & Dong, Z. Epigenetic regulation in AKI and kidney repair: mechanisms and therapeutic implications. Nat. Rev. Nephrol. 15, 220–239 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  53. Zhou, J., Chen, H. & Fan, Y. Systematic analysis of the expression profile of non-coding RNAs involved in ischemia/reperfusion-induced acute kidney injury in mice using RNA sequencing. Oncotarget 8, 100196–100215 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  54. Li, Y.-F. et al. MicroRNA-21 in the pathogenesis of acute kidney injury. Protein Cell 4, 813–819 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Liu, X. et al. MiR-21 inhibits autophagy by targeting Rab11a in renal ischemia/reperfusion. Exp. Cell Res. 338, 64–69 (2015).

    Article  CAS  PubMed  Google Scholar 

  56. Xu, X. et al. Delayed ischemic preconditioning contributes to renal protection by upregulation of miR-21. Kidney Int. 82, 1167–1175 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Hu, H., Jiang, W., Xi, X., Zou, C. & Ye, Z. MicroRNA-21 attenuates renal ischemia reperfusion injury via targeting caspase signaling in mice. Am. J. Nephrol. 40, 215–223 (2014).

    Article  CAS  PubMed  Google Scholar 

  58. Jia, P. et al. miR-21 contributes to xenon-conferred amelioration of renal ischemia-reperfusion injury in mice. Anesthesiology 119, 621–630 (2013).

    Article  CAS  PubMed  Google Scholar 

  59. Godwin, J. G. et al. Identification of a microRNA signature of renal ischemia reperfusion injury. Proc. Natl Acad. Sci. USA 107, 14339–14344 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Geng, X. et al. LncRNA GAS5 promotes apoptosis as a competing endogenous RNA for miR-21 via thrombospondin 1 in ischemic AKI. Cell Death Discov. 6, 19 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Song, N. et al. miR-21 protects against ischemia/reperfusion-induced acute kidney injury by preventing epithelial cell apoptosis and inhibiting dendritic cell maturation. Front. Physiol. 9, 790 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Wei, Q. et al. MicroRNA-489 induction by hypoxia-inducible factor-1 protects against ischemic kidney injury. J. Am. Soc. Nephrol. 27, 2784–2796 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Wei, Q. et al. MicroRNA-668 represses MTP18 to preserve mitochondrial dynamics in ischemic acute kidney injury. J. Clin. Invest. 128, 5448–5464 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  64. Hao, J. et al. Induction of microRNA-17-5p by p53 protects against renal ischemia-reperfusion injury by targeting death receptor 6. Kidney Int. 91, 106–118 (2017).

    Article  CAS  PubMed  Google Scholar 

  65. Kaucsár, T. et al. Activation of the miR-17 family and miR-21 during murine kidney ischemia-reperfusion injury. Nucleic Acid. Ther. 23, 344–354 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Chiba, T. et al. Endothelial-derived miR-1792 promotes angiogenesis to protect against renal ischemia-reperfusion injury. J. Am. Soc. Nephrol. 32, 553–562 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Song, T. et al. miR-17-92 ameliorates renal ischemia reperfusion injury. Kaohsiung J. Med. Sci. 34, 263–273 (2018).

    Article  PubMed  Google Scholar 

  68. Viñas, J. L. et al. Transfer of microRNA-486-5p from human endothelial colony forming cell-derived exosomes reduces ischemic kidney injury. Kidney Int. 90, 1238–1250 (2016).

    Article  PubMed  CAS  Google Scholar 

  69. Yue, J. et al. MicroRNA-187 reduces acute ischemic renal podocyte injury via targeting acetylcholinesterase. J. Surg. Res. 244, 302–311 (2019).

    Article  CAS  PubMed  Google Scholar 

  70. Chen, H.-H. et al. Urinary miR-16 transactivated by C/EBPβ reduces kidney function after ischemia/reperfusion-induced injury. Sci. Rep. 6, 27945 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Lorenzen, J. M. et al. MicroRNA-24 antagonism prevents renal ischemia reperfusion injury. J. Am. Soc. Nephrol. 25, 2717–2729 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Collier, J. B. & Schnellmann, R. G. Extracellular signal-regulated kinase 1/2 regulates NAD metabolism during acute kidney injury through microRNA-34a-mediated NAMPT expression. Cell. Mol. Life Sci. https://doi.org/10.1007/s00018-019-03391-z (2019).

    Article  PubMed  Google Scholar 

  73. Liu, X.-J. et al. MicroRNA-34a suppresses autophagy in tubular epithelial cells in acute kidney injury. Am. J. Nephrol. 42, 168–175 (2015).

    Article  CAS  PubMed  Google Scholar 

  74. Bhatt, K. et al. MicroRNA-687 induced by hypoxia-inducible factor-1 targets phosphatase and tensin homolog in renal ischemia-reperfusion injury. J. Am. Soc. Nephrol. 26, 1588–1596 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Wilflingseder, J. et al. miR-182-5p inhibition ameliorates ischemic acute kidney injury. Am. J. Pathol. 187, 70–79 (2017).

    Article  CAS  PubMed  Google Scholar 

  76. Li, H., Ma, Y., Chen, B. & Shi, J. miR-182 enhances acute kidney injury by promoting apoptosis involving the targeting and regulation of TCF7L2/Wnt/β-catenins pathway. Eur. J. Pharmacol. 831, 20–27 (2018).

    Article  CAS  PubMed  Google Scholar 

  77. Denby, L. et al. miR-21 and miR-214 are consistently modulated during renal injury in rodent models. Am. J. Pathol. 179, 661–672 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Denby, L. et al. MicroRNA-214 antagonism protects against renal fibrosis. J. Am. Soc. Nephrol. 25, 65–80 (2014).

    Article  CAS  PubMed  Google Scholar 

  79. Yan, Y. et al. miR-214 represses mitofusin-2 to promote renal tubular apoptosis in ischemic acute kidney injury. Am. J. Physiol. Renal Physiol. 318, F878–F887 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Zhu, X., Li, W. & Li, H. miR-214 ameliorates acute kidney injury via targeting DKK3 and activating of Wnt/β-catenin signaling pathway. Biol. Res. 51, 31 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Tian, X. et al. LINC00520 targeting miR-27b-3p regulates OSMR expression level to promote acute kidney injury development through the PI3K/AKT signaling pathway. J. Cell. Physiol. 234, 14221–14233 (2019).

    Article  CAS  PubMed  Google Scholar 

  82. Wang, Y., Wang, D. & Jin, Z. miR‑27a suppresses TLR4‑induced renal ischemia‑reperfusion injury. Mol. Med. Rep. 20, 967–976 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Zhang, C. et al. miR-30c-5p reduces renal ischemia-reperfusion involving macrophage. Med. Sci. Monit. 25, 4362–4369 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Dai, Y. et al. miR-146a is essential for lipopolysaccharide (LPS)-induced cross-tolerance against kidney ischemia/reperfusion injury in mice. Sci. Rep. 6, 27091 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Amrouche, L. et al. MicroRNA-146a in human and experimental ischemic AKI: CXCL8-dependent mechanism of action. J. Am. Soc. Nephrol. 28, 479–493 (2017).

    Article  CAS  PubMed  Google Scholar 

  86. Zhang, Y. et al. MiR-181d-5p targets KLF6 to improve ischemia/reperfusion-induced AKI through effects on renal function, apoptosis, and inflammation. Front. Physiol. 11, 510 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  87. Xu, Y. et al. miR-195-5p alleviates acute kidney injury through repression of inflammation and oxidative stress by targeting vascular endothelial growth factor A. Aging 12, 10235–10245 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Lan, Y.-F. et al. MicroRNA-494 reduces ATF3 expression and promotes AKI. J. Am. Soc. Nephrol. 23, 2012–2023 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Bijkerk, R. et al. Hematopoietic microRNA-126 protects against renal ischemia/reperfusion injury by promoting vascular integrity. J. Am. Soc. Nephrol. 25, 1710–1722 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Wang, X. et al. miR-218 expressed in endothelial progenitor cells contributes to the development and repair of the kidney microvasculature. Am. J. Pathol. 190, 642–659 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Ranganathan, P. et al. MicroRNA-150 deletion in mice protects kidney from myocardial infarction-induced acute kidney injury. Am. J. Physiol. Renal Physiol. 309, F551–F558 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Guan, H. et al. Injured tubular epithelial cells activate fibroblasts to promote kidney fibrosis through miR-150-containing exosomes. Exp. Cell Res. 392, 112007 (2020).

    Article  CAS  PubMed  Google Scholar 

  93. Hao, J. et al. MicroRNA-375 is induced in cisplatin nephrotoxicity to repress hepatocyte nuclear factor 1-β. J. Biol. Chem. 292, 4571–4582 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Pellegrini, K. L. et al. Application of small RNA sequencing to identify microRNAs in acute kidney injury and fibrosis. Toxicol. Appl. Pharmacol. 312, 42–52 (2016).

    Article  CAS  PubMed  Google Scholar 

  95. Zhang, C. et al. miRNA‑mRNA regulatory network analysis of mesenchymal stem cell treatment in cisplatin‑induced acute kidney injury identifies roles for miR‑210/Serpine1 and miR‑378/Fos in regulating inflammation. Mol. Med. Rep. 20, 1509–1522 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Huang, G., Xue, J., Sun, X., Wang, J. & Yu, L. L. Necroptosis in 3-chloro-1, 2-propanediol (3-MCPD)-dipalmitate-induced acute kidney injury in vivo and its repression by miR-223-3p. Toxicology 406–407, 33–43 (2018).

    Article  PubMed  CAS  Google Scholar 

  97. Bhatt, K. et al. MicroRNA-34a is induced via p53 during cisplatin nephrotoxicity and contributes to cell survival. Mol. Med. 16, 409–416 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Lee, C. G. et al. Discovery of an integrative network of microRNAs and transcriptomics changes for acute kidney injury. Kidney Int. 86, 943–953 (2014).

    Article  CAS  PubMed  Google Scholar 

  99. Liao, W. et al. MicroRNA-140-5p attenuated oxidative stress in cisplatin induced acute kidney injury by activating Nrf2/ARE pathway through a Keap1-independent mechanism. Exp. Cell Res. 360, 292–302 (2017).

    Article  CAS  PubMed  Google Scholar 

  100. Saikumar, J. et al. Expression, circulation, and excretion profile of microRNA-21, -155, and -18a following acute kidney injury. Toxicol. Sci. 129, 256–267 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Pellegrini, K. L. et al. MicroRNA-155 deficient mice experience heightened kidney toxicity when dosed with cisplatin. Toxicol. Sci. 141, 484–492 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Huang, S.-J. et al. The renoprotective effect of curcumin against cisplatin-induced acute kidney injury in mice: involvement of miR-181a/PTEN axis. Ren. Fail. 42, 350–357 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Yuan, J., Benway, C. J., Bagley, J. & Iacomini, J. MicroRNA-494 promotes cyclosporine-induced nephrotoxicity and epithelial to mesenchymal transition by inhibiting PTEN. Am. J. Transplant. 15, 1682–1691 (2015).

    Article  CAS  PubMed  Google Scholar 

  104. Yamashita, N. et al. Intratubular epithelial-mesenchymal transition and tubular atrophy after kidney injury in mice. Am. J. Physiol. Renal Physiol. 319, F579–F591 (2020).

    Article  CAS  PubMed  Google Scholar 

  105. Wang, J. et al. MBD2 upregulates miR-301a-5p to induce kidney cell apoptosis during vancomycin-induced AKI. Cell Death Dis. 8, e3120 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Guo, Y. et al. MicroRNA-709 mediates acute tubular injury through effects on mitochondrial function. J. Am. Soc. Nephrol. 29, 449–461 (2018).

    Article  CAS  PubMed  Google Scholar 

  107. Zhu, Y. et al. MicroRNA-146b, a sensitive indicator of mesenchymal stem cell repair of acute renal injury. Stem Cell Transl. Med. 5, 1406–1415 (2016).

    Article  CAS  Google Scholar 

  108. Liu, B. et al. MicroRNA-188 aggravates contrast-induced apoptosis by targeting SRSF7 in novel isotonic contrast-induced acute kidney injury rat models and renal tubular epithelial cells. Ann. Transl. Med. 7, 378 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Li, X.-Y., Zhang, K., Jiang, Z.-Y. & Cai, L.-H. MiR-204/miR-211 downregulation contributes to candidemia-induced kidney injuries via derepression of Hmx1 expression. Life Sci. 102, 139–144 (2014).

    Article  CAS  PubMed  Google Scholar 

  110. Ma, J., Li, Y.-T., Zhang, S.-X., Fu, S.-Z. & Ye, X.-Z. MiR-590-3p attenuates acute kidney injury by inhibiting tumor necrosis factor receptor-associated factor 6 in septic mice. Inflammation 42, 637–649 (2019).

    Article  CAS  PubMed  Google Scholar 

  111. He, S.-Y., Wang, G., Pei, Y.-H. & Zhu, H.-P. miR-34b-3p protects against acute kidney injury in sepsis mice via targeting ubiquitin-like protein 4A. Kaohsiung J. Med. Sci. https://doi.org/10.1002/kjm2.12255 (2020).

    Article  PubMed  Google Scholar 

  112. Lin, Z., Liu, Z., Wang, X., Qiu, C. & Zheng, S. MiR-21-3p plays a crucial role in metabolism alteration of renal tubular epithelial cells during sepsis associated acute kidney injury via AKT/CDK2-FOXO1 pathway. BioMed. Res. Int. 2019, 2821731 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  113. Pan, T. et al. Delayed remote ischemic preconditioning confers renoprotection against septic acute kidney injury via exosomal miR-21. Theranostics 9, 405–423 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Zhang, P. et al. The biomarker TCONS_00016233 drives septic AKI by targeting the miR-22-3p/AIFM1 signaling axis. Mol. Ther. Nucleic Acids 19, 1027–1042 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Ma, P., Zhang, C., Huo, P., Li, Y. & Yang, H. A novel role of the miR-152-3p/ERRFI1/STAT3 pathway modulates the apoptosis and inflammatory response after acute kidney injury. J. Biochem. Mol. Toxicol. https://doi.org/10.1002/jbt.22540 (2020).

    Article  PubMed  Google Scholar 

  116. Lu, S., Dong, L., Jing, X., Gen-Yang, C. & Zhan-Zheng, Z. Abnormal lncRNA CCAT1/microRNA-155/SIRT1 axis promoted inflammatory response and apoptosis of tubular epithelial cells in LPS caused acute kidney injury. Mitochondrion 53, 76–90 (2020).

    Article  PubMed  CAS  Google Scholar 

  117. Jiang, Z.-J., Zhang, M.-Y., Fan, Z.-W., Sun, W.-L. & Tang, Y. Influence of lncRNA HOTAIR on acute kidney injury in sepsis rats through regulating miR-34a/Bcl-2 pathway. Eur. Rev. Med. Pharmacol. Sci. 23, 3512–3519 (2019).

    PubMed  Google Scholar 

  118. Shen, Y., Yu, J., Jing, Y. & Zhang, J. MiR-106a aggravates sepsis-induced acute kidney injury by targeting THBS2 in mice model. Acta Cir. Bras. 34, e201900602 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  119. Wu, H., Wang, J. & Ma, Z. Long noncoding RNA HOXA-AS2 mediates microRNA-106b-5p to repress sepsis-engendered acute kidney injury. J. Biochem. Mol. Toxicol. 34, e22453 (2020).

    Article  CAS  PubMed  Google Scholar 

  120. Yan, Z., Zang, B., Gong, X., Ren, J. & Wang, R. MiR-214-3p exacerbates kidney damages and inflammation induced by hyperlipidemic pancreatitis complicated with acute renal injury. Life Sci. 241, 117118 (2020).

    Article  CAS  PubMed  Google Scholar 

  121. Sang, Z., Dong, S., Zhang, P. & Wei, Y. miR‑214 ameliorates sepsis‑induced acute kidney injury via PTEN/AKT/mTOR‑regulated autophagy. Mol. Med. Rep. 24, 683 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Guo, C. et al. MicroRNA-214-5p aggravates sepsis-related acute kidney injury in mice. Drug Dev. Res. https://doi.org/10.1002/ddr.21863 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  123. Wang, S., Zhang, Z., Wang, J. & Miao, H. MiR-107 induces TNF-α secretion in endothelial cells causing tubular cell injury in patients with septic acute kidney injury. Biochem. Biophys. Res. Commun. 483, 45–51 (2017).

    Article  CAS  PubMed  Google Scholar 

  124. Colbert, J. F. et al. A model-specific role of microRNA-223 as a mediator of kidney injury during experimental sepsis. Am. J. Physiol. Renal Physiol. 313, F553–F559 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Zheng, G., Qu, H., Li, F., Ma, W. & Yang, H. Propofol attenuates sepsis-induced acute kidney injury by regulating miR-290-5p/CCL-2 signaling pathway. Braz. J. Med. Biol. Res. 51, e7655 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Zhang, T. & Xiang, L. Honokiol alleviates sepsis-induced acute kidney injury in mice by targeting the miR-218-5p/heme oxygenase-1 signaling pathway. Cell. Mol. Biol. Lett. 24, 15 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  127. Li, X.-Y., Zhang, Y.-Q., Xu, G., Li, S.-H. & Li, H. miR-124/MCP-1 signaling pathway modulates the protective effect of itraconazole on acute kidney injury in a mouse model of disseminated candidiasis. Int. J. Mol. Med. 41, 3468–3476 (2018).

    CAS  PubMed  Google Scholar 

  128. Chen, X., Zhao, L., Xing, Y. & Lin, B. Down-regulation of microRNA-21 reduces inflammation and podocyte apoptosis in diabetic nephropathy by relieving the repression of TIMP3 expression. Biomed. Pharmacother. 108, 7–14 (2018).

    Article  CAS  PubMed  Google Scholar 

  129. Kölling, M. et al. Therapeutic miR-21 silencing ameliorates diabetic kidney disease in mice. Mol. Ther. 25, 165–180 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  130. McClelland, A. D. et al. miR-21 promotes renal fibrosis in diabetic nephropathy by targeting PTEN and SMAD7. Clin. Sci. 129, 1237–1249 (2015).

    Article  CAS  Google Scholar 

  131. Wang, J. et al. Atrasentan alleviates high glucose-induced podocyte injury by the microRNA-21/forkhead box O1 axis. Eur. J. Pharmacol. 852, 142–150 (2019).

    Article  CAS  PubMed  Google Scholar 

  132. Wang, J. et al. Serum miR-21 may be a potential diagnostic biomarker for diabetic nephropathy. Exp. Clin. Endocrinol. Diabetes 124, 417–423 (2016).

    PubMed  Google Scholar 

  133. Li, R., Chung, A. C. K., Yu, X. & Lan, H. Y. MicroRNAs in diabetic kidney disease. Int. J. Endocrinol. 2014, 1–11 (2014).

    Google Scholar 

  134. Sakuma, H., Hagiwara, S., Kantharidis, P., Gohda, T. & Suzuki, Y. Potential targeting of renal fibrosis in diabetic kidney disease using microRNAs. Front. Pharmacol. 11, 587689 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Yarahmadi, A., Shahrokhi, S. Z., Mostafavi-Pour, Z. & Azarpira, N. MicroRNAs in diabetic nephropathy: from molecular mechanisms to new therapeutic targets of treatment. Biochem. Pharmacol. 189, 114301 (2021).

    Article  CAS  PubMed  Google Scholar 

  136. Hsu, Y.-C. et al. Protective effects of miR-29a on diabetic glomerular dysfunction by modulation of DKK1/Wnt/β-catenin signaling. Sci. Rep. 6, 30575 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Srivastava, S. P. et al. Effect of antifibrotic microRNAs crosstalk on the action of N-acetyl-seryl-aspartyl-lysyl-proline in diabetes-related kidney fibrosis. Sci. Rep. 6, 29884 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Zhou, L. et al. High glucose induces renal tubular epithelial injury via Sirt1/NF-kappaB/microR-29/Keap1 signal pathway. J. Transl. Med. 13, 352 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  139. Sun, S. F. et al. Novel lncRNA Erbb4-IR promotes diabetic kidney injury in db/db mice by targeting miR-29b. Diabetes 67, 731–744 (2018).

    Article  CAS  PubMed  Google Scholar 

  140. Tung, C.-W. et al. MicroRNA-29a attenuates diabetic glomerular injury through modulating cannabinoid receptor 1 signaling. Molecules 24, 264 (2019).

    Article  PubMed Central  CAS  Google Scholar 

  141. Zhou, Z. et al. MicroRNA-27a promotes podocyte injury via PPARγ-mediated β-catenin activation in diabetic nephropathy. Cell Death Dis. 8, e2658 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Hou, X. et al. MicroRNA-27a promotes renal tubulointerstitial fibrosis via suppressing PPARγ pathway in diabetic nephropathy. Oncotarget 7, 47760–47776 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  143. Wu, L. et al. MicroRNA-27a induces mesangial cell injury by targeting of PPARγ, and its in vivo knockdown prevents progression of diabetic nephropathy. Sci. Rep. 6, 26072 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Song, J. et al. Omentin-1 protects renal function of mice with type 2 diabetic nephropathy via regulating miR-27a-Nrf2/Keap1 axis. Biomed. Pharmacother. 107, 440–446 (2018).

    Article  CAS  PubMed  Google Scholar 

  145. Bai, X. et al. Long noncoding RNA LINC01619 regulates microRNA-27a/forkhead box protein O1 and endoplasmic reticulum stress-mediated podocyte injury in diabetic nephropathy. Antioxid. Redox Signal. 29, 355–376 (2018).

    Article  CAS  PubMed  Google Scholar 

  146. Zhao, B. et al. MicroRNA-23b targets Ras GTPase-activating protein SH3 domain-binding protein 2 to alleviate fibrosis and albuminuria in diabetic nephropathy. J. Am. Soc. Nephrol. 27, 2597–2608 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  147. Liu, H. et al. Effects and mechanism of miR-23b on glucose-mediated epithelial-to-mesenchymal transition in diabetic nephropathy. Int. J. Biochem. Cell Biol. 70, 149–160 (2016).

    Article  CAS  PubMed  Google Scholar 

  148. Li, X. et al. Long noncoding RNA MALAT1 regulates renal tubular epithelial pyroptosis by modulated miR-23c targeting of ELAVL1 in diabetic nephropathy. Exp. Cell Res. 350, 327–335 (2017).

    Article  CAS  PubMed  Google Scholar 

  149. Liu, Y. et al. Variations in microRNA-25 expression influence the severity of diabetic kidney disease. J. Am. Soc. Nephrol. 28, 3627–3638 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Oh, H. J. et al. Inhibition of the processing of miR-25 by HIPK2-Phosphorylated-MeCP2 induces NOX4 in early diabetic nephropathy. Sci. Rep. 6, 38789 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Zhao, Y. et al. MiR‐30c protects diabetic nephropathy by suppressing epithelial‐to‐mesenchymal transition in db/db mice. Aging Cell 16, 387–400 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Zheng, Z. et al. The coordinated roles of miR-26a and miR-30c in regulating TGFβ1-induced epithelial-to-mesenchymal transition in diabetic nephropathy. Sci. Rep. 6, 37492 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Koga, K. et al. MicroRNA-26a inhibits TGF-β-induced extracellular matrix protein expression in podocytes by targeting CTGF and is downregulated in diabetic nephropathy. Diabetologia 58, 2169–2180 (2015).

    Article  CAS  PubMed  Google Scholar 

  154. Liu, W.-T. et al. Metadherin facilitates podocyte apoptosis in diabetic nephropathy. Cell Death Dis. 7, e2477 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Zhao, D., Jia, J. & Shao, H. miR-30e targets GLIPR-2 to modulate diabetic nephropathy: in vitro and in vivo experiments. J. Mol. Endocrinol. 59, 181–190 (2017).

    Article  CAS  PubMed  Google Scholar 

  156. Wang, J. et al. Downregulation of miR-30c promotes renal fibrosis by target CTGF in diabetic nephropathy. J. Diabetes Complicat. 30, 406–414 (2016).

    Article  Google Scholar 

  157. Sun, Z. et al. miR-133b and miR-199b knockdown attenuate TGF-β1-induced epithelial to mesenchymal transition and renal fibrosis by targeting SIRT1 in diabetic nephropathy. Eur. J. Pharmacol. 837, 96–104 (2018).

    Article  CAS  PubMed  Google Scholar 

  158. Kang, W.-L. & Xu, G.-S. Atrasentan increased the expression of klotho by mediating miR-199b-5p and prevented renal tubular injury in diabetic nephropathy. Sci. Rep. 6, 19979 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Badal, S. S. et al. miR-93 regulates Msk2-mediated chromatin remodelling in diabetic nephropathy. Nat. Commun. 7, 12076 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Yang, J. et al. Silencing of long noncoding RNA XIST protects against renal interstitial fibrosis in diabetic nephropathy via microRNA-93-5p-mediated inhibition of CDKN1A. Am. J. Physiol. Renal Physiol. 317, F1350–F1358 (2019).

    Article  CAS  PubMed  Google Scholar 

  161. Sun, Y. et al. miR-451 suppresses the NF-kappaB-mediated proinflammatory molecules expression through inhibiting LMP7 in diabetic nephropathy. Mol. Cell. Endocrinol. 433, 75–86 (2016).

    Article  CAS  PubMed  Google Scholar 

  162. Mohan, A. et al. Urinary exosomal microRNA-451-5p is a potential early biomarker of diabetic nephropathy in rats. PLoS One 11, e0154055 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  163. Zhang, Y. et al. The long noncoding RNA 150Rik promotes mesangial cell proliferation via miR-451/IGF1R/p38 MAPK signaling in diabetic nephropathy. Cell. Physiol. Biochem. 51, 1410–1428 (2018).

    Article  CAS  PubMed  Google Scholar 

  164. Lee, H. W. et al. Absence of miR-146a in podocytes increases risk of diabetic glomerulopathy via up-regulation of ErbB4 and Notch-1. J. Biol. Chem. 292, 732–747 (2017).

    Article  CAS  PubMed  Google Scholar 

  165. Oghbaei, H., Ahmadi Asl, N. & Sheikhzadeh, F. Can regular moderate exercise lead to changes in miRNA-146a and its adapter proteins in the kidney of streptozotocin-induced diabetic male rats? Endocr. Regul. 51, 145–152 (2017).

    Article  CAS  PubMed  Google Scholar 

  166. Wan, R. J. & Li, Y. H. MicroRNA‑146a/NAPDH oxidase4 decreases reactive oxygen species generation and inflammation in a diabetic nephropathy model. Mol. Med. Rep. 17, 4759–4766 (2018).

    CAS  PubMed  Google Scholar 

  167. Chen, S., Feng, B., Thomas, A. A. & Chakrabarti, S. miR-146a regulates glucose induced upregulation of inflammatory cytokines extracellular matrix proteins in the retina and kidney in diabetes. PLoS One 12, e0173918 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  168. Tsai, Y.-C. et al. Angpt2 induces mesangial cell apoptosis through the microRNA-33-5p-SOCS5 loop in diabetic nephropathy. Mol. Ther. Nucleic Acids 13, 543–555 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Bai, X., Geng, J., Zhou, Z., Tian, J. & Li, X. MicroRNA-130b improves renal tubulointerstitial fibrosis via repression of Snail-induced epithelial-mesenchymal transition in diabetic nephropathy. Sci. Rep. 6, 20475 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Hajarnis, S. et al. microRNA-17 family promotes polycystic kidney disease progression through modulation of mitochondrial metabolism. Nat. Commun. 8, 14395 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Yheskel, M., Lakhia, R., Cobo-Stark, P., Flaten, A. & Patel, V. Anti-microRNA screen uncovers miR-17 family within miR-17~92 cluster as the primary driver of kidney cyst growth. Sci. Rep. 9, 1920 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  172. Lakhia, R. et al. MicroRNA-21 aggravates cyst growth in a model of polycystic kidney disease. J. Am. Soc. Nephrol. 27, 2319–2330 (2016).

    Article  CAS  PubMed  Google Scholar 

  173. Woo, Y. M. et al. Profiling of miRNAs and target genes related to cystogenesis in ADPKD mouse models. Sci. Rep. 7, 14151 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  174. Lakhia, R. et al. Interstitial microRNA miR-214 attenuates inflammation and polycystic kidney disease progression. JCI Insight https://doi.org/10.1172/jci.insight.133785 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  175. Kim, D. Y. et al. Impact of miR-192 and miR-194 on cyst enlargement through EMT in autosomal dominant polycystic kidney disease. FASEB J. 33, 2870–2884 (2019).

    Article  CAS  PubMed  Google Scholar 

  176. Magayr, T. A. et al. Global microRNA profiling in human urinary exosomes reveals novel disease biomarkers and cellular pathways for autosomal dominant polycystic kidney disease. Kidney Int. 98, 420–435 (2020).

    Article  CAS  PubMed  Google Scholar 

  177. Streets, A. J. et al. Parallel microarray profiling identifies ErbB4 as a determinant of cyst growth in ADPKD and a prognostic biomarker for disease progression. Am. J. Physiol. Renal Physiol. 312, F577–F588 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Shin, Y., Kim, D. Y., Ko, J. Y., Woo, Y. M. & Park, J. H. Regulation of KLF12 by microRNA-20b and microRNA-106a in cystogenesis. FASEB J. 32, 3574–3582 (2018).

    Article  CAS  PubMed  Google Scholar 

  179. Liu, G. et al. miR-25-3p promotes proliferation and inhibits autophagy of renal cells in polycystic kidney mice by regulating ATG14-Beclin 1. Ren. Fail. 42, 333–342 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Han, X. et al. MicroRNA-130b ameliorates murine lupus nephritis through targeting the type I interferon pathway on renal mesangial cells. Arthritis Rheumatol. 68, 2232–2243 (2016).

    Article  CAS  PubMed  Google Scholar 

  181. Liu, D. et al. MiR-130a-5p prevents angiotensin II-induced podocyte apoptosis by modulating M-type phospholipase A2 receptor. Cell Cycle 17, 2484–2495 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Costa-Reis, P. et al. The role of microRNAs and human epidermal growth factor receptor 2 in proliferative lupus nephritis. Arthritis Rheumatol. 67, 2415–2426 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Peng, R. et al. MiR-30a inhibits the epithelial–mesenchymal transition of podocytes through downregulation of NFATc3. Int. J. Mol. Sci. 16, 24032–24047 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Wu, J. et al. MicroRNA-30 family members regulate calcium/calcineurin signaling in podocytes. J. Clin. Invest. 125, 4091–4106 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  185. Müller-Deile, J. et al. Podocytes regulate the glomerular basement membrane protein nephronectin by means of miR-378a-3p in glomerular diseases. Kidney Int. 92, 836–849 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  186. Hu, S. et al. The long noncoding RNA LOC105374325 causes podocyte injury in individuals with focal segmental glomerulosclerosis. J. Biol. Chem. 293, 20227–20239 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Xin, Q. et al. miR-155 deficiency ameliorates autoimmune inflammation of systemic lupus erythematosus by targeting S1pr1 in Faslpr/lpr mice. J. Immunol. 194, 5437–5445 (2015).

    Article  CAS  PubMed  Google Scholar 

  188. Lin, X. et al. Role of MiR-155 signal pathway in regulating podocyte injury induced by TGF-β1. Cell. Physiol. Biochem. 42, 1469–1480 (2017).

    Article  CAS  PubMed  Google Scholar 

  189. Cai, Z. et al. MicroRNA-145 involves in the pathogenesis of renal vascular lesions and may become a potential therapeutic target in patients with juvenile lupus nephritis. Kidney Blood Press. Res. 44, 643–655 (2019).

    Article  CAS  PubMed  Google Scholar 

  190. Wu, J. et al. MiR-145-5p inhibits proliferation and inflammatory responses of RMC through regulating AKT/GSK pathway by targeting CXCL16. J. Cell. Physiol. 233, 3648–3659 (2018).

    Article  CAS  PubMed  Google Scholar 

  191. Ye, H. et al. microRNA-199a may be involved in the pathogenesis of lupus nephritis via modulating the activation of NF-κB by targeting Klotho. Mol. Immunol. 103, 235–242 (2018).

    Article  CAS  PubMed  Google Scholar 

  192. Yang, R. et al. p53 induces miR199a-3p to suppress SOCS7 for STAT3 activation and renal fibrosis in UUO. Sci. Rep. 7, 43409 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  193. Sheng, Z.-X., Yao, H. & Cai, Z.-Y. The role of miR-146b-5p in TLR4 pathway of glomerular mesangial cells with lupus nephritis. Eur. Rev. Med. Pharmacol. Sci. 22, 1737–1743 (2018).

    PubMed  Google Scholar 

  194. Amrouche, L. et al. MicroRNA-146a-deficient mice develop immune complex glomerulonephritis. Sci. Rep. 9, 15597 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  195. Qingjuan, L. et al. miR-148a-3p overexpression contributes to glomerular cell proliferation by targeting PTEN in lupus nephritis. Am. J. Physiol. Cell Physiol. 310, C470–C478 (2016).

    Article  PubMed  Google Scholar 

  196. Krasoudaki, E. et al. Micro-RNA analysis of renal biopsies in human lupus nephritis demonstrates up-regulated miR-422a driving reduction of kallikrein-related peptidase 4. Nephrol. Dial. Transplant. 31, 1676–1686 (2016).

    Article  CAS  PubMed  Google Scholar 

  197. Pusey, C. D. Anti-glomerular basement membrane disease. Kidney Int. 64, 1535–1550 (2003).

    Article  PubMed  Google Scholar 

  198. Henique, C. et al. Genetic and pharmacological inhibition of microRNA-92a maintains podocyte cell cycle quiescence and limits crescentic glomerulonephritis. Nat. Commun. 8, 1829 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  199. Kietzmann, L. et al. MicroRNA-193a regulates the transdifferentiation of human parietal epithelial cells toward a podocyte phenotype. J. Am. Soc. Nephrol. 26, 1389–1401 (2015).

    Article  CAS  PubMed  Google Scholar 

  200. Gebeshuber, C. A. et al. Focal segmental glomerulosclerosis is induced by microRNA-193a and its downregulation of WT1. Nat. Med. 19, 481–487 (2013).

    Article  CAS  PubMed  Google Scholar 

  201. Lu, Q. et al. Circulating miR-103a-3p contributes to angiotensin II-induced renal inflammation and fibrosis via a SNRK/NF-κB/p65 regulatory axis. Nat. Commun. 10, 2145 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  202. Yao, C. et al. Sublytic C5b-9 induces glomerular mesangial cell apoptosis through miR-3546/SOX4/survivin axis in rat Thy-1 nephritis. Cell. Physiol. Biochem. 49, 1898–1917 (2018).

    Article  CAS  PubMed  Google Scholar 

  203. Jin, L. et al. Down-regulation of the long non-coding RNA XIST ameliorates podocyte apoptosis in membranous nephropathy via the miR-217–TLR4 pathway. Exp. Physiol. 104, 220–230 (2019).

    CAS  PubMed  Google Scholar 

  204. Tinel, C., Lamarthée, B. & Anglicheau, D. MicroRNAs: small molecules, big effects. Curr. Opin. Organ. Transplant. https://doi.org/10.1097/MOT.0000000000000835 (2020).

    Article  Google Scholar 

  205. Uehara, M. et al. Ischemia augments alloimmune injury through IL-6-driven CD4+ alloreactivity. Sci. Rep. 8, 2461 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  206. Ledeganck, K. J. et al. MicroRNAs in AKI and kidney transplantation. Clin. J. Am. Soc. Nephrol. 14, 454–468 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  207. Halloran, P. F., Famulski, K. S. & Reeve, J. Molecular assessment of disease states in kidney transplant biopsy samples. Nat. Rev. Nephrol. 12, 534–548 (2016).

    Article  CAS  PubMed  Google Scholar 

  208. Misra, M. K., Pandey, S. K., Kapoor, R., Sharma, R. K. & Agrawal, S. Genetic variants of microRNA-related genes in susceptibility and prognosis of end-stage renal disease and renal allograft outcome among north Indians. Pharmacogenet. Genomics 24, 442–450 (2014).

    Article  CAS  PubMed  Google Scholar 

  209. Oetting, W. S. et al. Analysis of 75 candidate SNPs associated with acute rejection in kidney transplant recipients: validation of rs2910164 in microRNA MIR146A. Transplantation 103, 1591–1602 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  210. Liu, X. et al. MicroRNA-10b downregulation mediates acute rejection of renal allografts by derepressing BCL2L11. Exp. Cell Res. 333, 155–163 (2015).

    Article  CAS  PubMed  Google Scholar 

  211. Yu, Y. et al. Bim is required for T-cell allogeneic responses and graft-versus-host disease in vivo. Am. J. Blood Res. 2, 77–85 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  212. Sheppard, H. M. et al. MicroRNA regulation in human CD8+ T cell subsets — cytokine exposure alone drives miR-146a expression. J. Transl. Med. 12, 292 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  213. Lu, L.-F. et al. Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses. Cell 142, 914–929 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  214. Ouyang, W. et al. Novel Foxo1-dependent transcriptional programs control T(reg) cell function. Nature 491, 554–559 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Wilflingseder, J. et al. Molecular pathogenesis of post-transplant acute kidney injury: assessment of whole-genome mRNA and miRNA profiles. PLoS One 9, e104164 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  216. Wei, L. et al. Differential expression of microRNAs during allograft rejection. Am. J. Transplant. 12, 1113–1123 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  217. Wei, L. et al. Absence of miR-182 augments cardiac allograft survival. Transplantation 101, 524–530 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  218. Anandagoda, N. et al. Dominant regulation of long-term allograft survival is mediated by microRNA-142. Am. J. Transplant. 20, 2715–2727 (2020).

    Article  CAS  PubMed  Google Scholar 

  219. Anandagoda, N. et al. microRNA-142-mediated repression of phosphodiesterase 3B critically regulates peripheral immune tolerance. J. Clin. Invest. 129, 1257–1271 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  220. Meng, X.-M., Nikolic-Paterson, D. J. & Lan, H. Y. TGF-β: the master regulator of fibrosis. Nat. Rev. Nephrol. 12, 325–338 (2016).

    Article  CAS  PubMed  Google Scholar 

  221. Mehta, A. & Baltimore, D. MicroRNAs as regulatory elements in immune system logic. Nat. Rev. Immunol. 16, 279–294 (2016).

    Article  CAS  PubMed  Google Scholar 

  222. Banerjee, S. et al. MicroRNA let-7c regulates macrophage polarization. J. Immunol. 190, 6542–6549 (2013).

    Article  CAS  PubMed  Google Scholar 

  223. Zhang, W., Liu, H., Liu, W., Liu, Y. & Xu, J. Polycomb-mediated loss of microRNA let-7c determines inflammatory macrophage polarization via PAK1-dependent NF-κB pathway. Cell Death Differ. 22, 287–297 (2015).

    Article  CAS  PubMed  Google Scholar 

  224. Hamdorf, M., Kawakita, S. & Everly, M. The potential of microRNAs as novel biomarkers for transplant rejection. J. Immunol. Res. 2017, 4072364 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  225. Wang, B. et al. Transforming growth factor-β1-mediated renal fibrosis is dependent on the regulation of transforming growth factor receptor 1 expression by let-7b. Kidney Int. 85, 352–361 (2014).

    Article  CAS  PubMed  Google Scholar 

  226. Racusen, L. C. & Regele, H. The pathology of chronic allograft dysfunction. Kidney Int. Suppl. https://doi.org/10.1038/ki.2010.419 (2010).

    Article  PubMed  Google Scholar 

  227. Loboda, A., Sobczak, M., Jozkowicz, A. & Dulak, J. TGF-β1/Smads and miR-21 in renal fibrosis and inflammation. Mediators Inflamm. 2016, 8319283 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  228. Gupta, S. K. et al. miR-21 promotes fibrosis in an acute cardiac allograft transplantation model. Cardiovasc. Res. 110, 215–226 (2016).

    Article  CAS  PubMed  Google Scholar 

  229. Glover, E. K., Jordan, N., Sheerin, N. S. & Ali, S. Regulation of endothelial-to-mesenchymal transition by microRNAs in chronic allograft dysfunction. Transplantation 103, e64–e73 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  230. Van Aelst, L. N. L. et al. RNA profiling in human and murine transplanted hearts: identification and validation of therapeutic targets for acute cardiac and renal allograft rejection. Am. J. Transplant. 16, 99–110 (2016).

    Article  PubMed  CAS  Google Scholar 

  231. Amrouche, L., Rabant, M. & Anglicheau, D. MicroRNAs as biomarkers of graft outcome. Transplant. Rev. 28, 111–118 (2014).

    Article  Google Scholar 

  232. van de Vrie, M., Deegens, J. K., Eikmans, M., van der Vlag, J. & Hilbrands, L. B. Urinary microRNA as biomarker in renal transplantation. Am. J. Transplant. 17, 1160–1166 (2017).

    Article  PubMed  CAS  Google Scholar 

  233. Khan, Z., Suthanthiran, M. & Muthukumar, T. MicroRNAs and transplantation. Clin. Lab. Med. 39, 125–143 (2019).

    Article  PubMed  Google Scholar 

  234. Sui, W. et al. Microarray analysis of microRNA expression in acute rejection after renal transplantation. Transpl. Immunol. 19, 81–85 (2008).

    Article  CAS  PubMed  Google Scholar 

  235. Lorenzen, J. M. et al. Urinary miR-210 as a mediator of acute T-cell mediated rejection in renal allograft recipients. Am. J. Transpl. 11, 2221–2227 (2011).

    Article  CAS  Google Scholar 

  236. Soltaninejad, E. et al. Differential expression of microRNAs in renal transplant patients with acute T-cell mediated rejection. Transpl. Immunol. 33, 1–6 (2015).

    Article  CAS  PubMed  Google Scholar 

  237. Matz, M. et al. Identification of T cell-mediated vascular rejection after kidney transplantation by the combined measurement of 5 specific microRNAs in blood. Transplantation 100, 898–907 (2016).

    Article  CAS  PubMed  Google Scholar 

  238. Millán, O. et al. Urinary miR-155-5p and CXCL10 as prognostic and predictive biomarkers of rejection, graft outcome and treatment response in kidney transplantation. Br. J. Clin. Pharmacol. 83, 2636–2650 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  239. Anglicheau, D. et al. MicroRNA expression profiles predictive of human renal allograft status. Proc. Natl Acad. Sci. USA 106, 5330–5335 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  240. Matz, M. et al. MicroRNA regulation in blood cells of renal transplanted patients with interstitial fibrosis/tubular atrophy and antibody-mediated rejection. PLoS One 13, e0201925 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  241. Danger, R. et al. Expression of miR-142-5p in peripheral blood mononuclear cells from renal transplant patients with chronic antibody-mediated rejection. PLoS One 8, e60702 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  242. Rascio, F. et al. A type I interferon signature characterizes chronic antibody-mediated rejection in kidney transplantation. J. Pathol. 237, 72–84 (2015).

    Article  CAS  PubMed  Google Scholar 

  243. Loupy, A., Hill, G. S. & Jordan, S. C. The impact of donor-specific anti-HLA antibodies on late kidney allograft failure. Nat. Rev. Nephrol. 8, 348–357 (2012).

    Article  CAS  PubMed  Google Scholar 

  244. Delville, M. et al. Early acute microvascular kidney transplant rejection in the absence of anti-HLA antibodies is associated with preformed IgG antibodies against diverse glomerular endothelial cell antigens. J. Am. Soc. Nephrol. https://doi.org/10.1681/ASN.2018080868 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  245. Bijkerk, R. et al. Acute rejection after kidney transplantation associates with circulating microRNAs and vascular injury. Transplant. Direct 3, e174 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  246. Chen, Y. & Gorski, D. H. Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5. Blood 111, 1217–1226 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  247. Scian, M. J. et al. MicroRNA profiles in allograft tissues and paired urines associate with chronic allograft dysfunction with IF/TA. Am. J. Transplant. 11, 2110–2122 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  248. Ben-Dov, I. Z. et al. MicroRNA sequence profiles of human kidney allografts with or without tubulointerstitial fibrosis. Transplantation 94, 1086–1094 (2012).

    Article  CAS  PubMed  Google Scholar 

  249. Zununi Vahed, S. et al. Differential expression of circulating miR-21, miR-142-3p and miR-155 in renal transplant recipients with impaired graft function. Int. Urol. Nephrol. 49, 1681–1689 (2017).

    Article  CAS  PubMed  Google Scholar 

  250. Maluf, D. G. et al. The urine microRNA profile may help monitor post-transplant renal graft function. Kidney Int. 85, 439–449 (2014).

    Article  CAS  PubMed  Google Scholar 

  251. Vitalone, M. J. et al. Transcriptional perturbations in graft rejection. Transplantation 99, 1882–1893 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  252. Nariman-Saleh-Fam, Z. et al. Cell-free microRNA-148a is associated with renal allograft dysfunction: implication for biomarker discovery. J. Cell. Biochem. 120, 5737–5746 (2019).

    Article  CAS  PubMed  Google Scholar 

  253. McGuinness, D. et al. Identification of molecular markers of delayed graft function based on the regulation of biological ageing. PLoS One 11, e0146378 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  254. Bontha, S. V. et al. Effects of DNA methylation on progression to interstitial fibrosis and tubular atrophy in renal allograft biopsies: a multi-omics approach. Am. J. Transplant. 17, 3060–3075 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  255. Ichii, O. & Horino, T. MicroRNAs associated with the development of kidney diseases in humans and animals. J. Toxicol. Pathol. 31, 23–34 (2018).

    Article  CAS  PubMed  Google Scholar 

  256. Metzinger-Le Meuth, V. & Metzinger, L. miR-223 and other miRNA’s evaluation in chronic kidney disease: innovative biomarkers and therapeutic tools. Noncoding RNA Res. 4, 30–35 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  257. Chung, A. C., Yu, X. & Lan, H. Y. MicroRNA and nephropathy: emerging concepts. Int. J. Nephrol. Renov. Dis. 6, 169–179 (2013).

    CAS  Google Scholar 

  258. Beltrami, C. et al. Association of elevated urinary miR-126, miR-155, and miR-29b with diabetic kidney disease. Am. J. Pathol. 188, 1982–1992 (2018).

    Article  CAS  PubMed  Google Scholar 

  259. Park, S. et al. Urinary and blood microRNA-126 and -770 are potential noninvasive biomarker candidates for diabetic nephropathy: a meta-analysis. Cell. Physiol. Biochem. 46, 1331–1340 (2018).

    Article  CAS  PubMed  Google Scholar 

  260. Watany, M. M., Hagag, R. Y. & Okda, H. I. Circulating miR-21, miR-210 and miR-146a as potential biomarkers to differentiate acute tubular necrosis from hepatorenal syndrome in patients with liver cirrhosis: a pilot study. Clin. Chem. Lab. Med. 56, 739–747 (2018).

    Article  CAS  PubMed  Google Scholar 

  261. Dong, C. et al. Circulating exosomes derived-miR-146a from systemic lupus erythematosus patients regulates senescence of mesenchymal stem cells. BioMed. Res. Int. 2019, 6071308 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  262. Pavkovic, M. et al. Detection of drug-induced acute kidney injury in humans using urinary KIM-1, miR-21, -200c, and -423. Toxicol. Sci. 152, 205–213 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  263. Ramachandran, K. et al. Human miRNome profiling identifies microRNAs differentially present in the urine after kidney injury. Clin. Chem. 59, 1742–1752 (2013).

    Article  CAS  PubMed  Google Scholar 

  264. Zhang, J., Wang, C.-J., Tang, X.-M. & Wei, Y.-K. Urinary miR-26b as a potential biomarker for patients with sepsis-associated acute kidney injury: a Chinese population-based study. Eur. Rev. Med. Pharmacol. Sci. 22, 4604–4610 (2018).

    CAS  PubMed  Google Scholar 

  265. Lorenzen, J. M. et al. Circulating miR-210 predicts survival in critically ill patients with acute kidney injury. Clin. J. Am. Soc. Nephrol. 6, 1540–1546 (2011).

    Article  CAS  PubMed  Google Scholar 

  266. Mousavi, M. Z. et al. Urinary micro-RNA biomarker detection using capped gold nanoslit SPR in a microfluidic chip. Analyst 140, 4097–4104 (2015).

    Article  CAS  PubMed  Google Scholar 

  267. Lange, T. et al. Identification of miR-16 as an endogenous reference gene for the normalization of urinary exosomal miRNA expression data from CKD patients. PLoS One 12, e0183435 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  268. Muralidharan, J. et al. Extracellular microRNA signature in chronic kidney disease. Am. J. Physiol. Renal Physiol. 312, F982–F991 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  269. Nandakumar, P. et al. MicroRNAs in the miR-17 and miR-15 families are downregulated in chronic kidney disease with hypertension. PLoS One 12, e0176734 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  270. Xiao, B. et al. Plasma microRNA panel is a novel biomarker for focal segmental glomerulosclerosis and associated with podocyte apoptosis. Cell Death Dis. 9, 533 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  271. Navarro-Quiroz, E. et al. Profiling analysis of circulating microRNA in peripheral blood of patients with class IV lupus nephritis. PLoS One 12, e0187973 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  272. Cui, C., Cui, Y., Fu, Y., Ma, S. & Zhang, S. Microarray analysis reveals gene and microRNA signatures in diabetic kidney disease. Mol. Med. Rep. 17, 2161–2168 (2018).

    CAS  PubMed  Google Scholar 

  273. Szeto, C.-C. et al. Urinary miRNA profile for the diagnosis of IgA nephropathy. BMC Nephrol. 20, 77 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  274. Xie, Y. et al. Urinary exosomal microRNA profiling in incipient type 2 diabetic kidney disease. J. Diabetes Res. 2017, 6978984 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  275. An, Y. et al. Increased urinary miR-196a level predicts the progression of renal injury in patients with diabetic nephropathy. Nephrol. Dial. Transplant. https://doi.org/10.1093/ndt/gfy326 (2018).

    Article  Google Scholar 

  276. Zhang, C. et al. Urinary miR-196a predicts disease progression in patients with chronic kidney disease. J. Transl. Med. 16, 91 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  277. Eissa, S., Matboli, M. & Bekhet, M. M. Clinical verification of a novel urinary microRNA panel: 133b, -342 and -30 as biomarkers for diabetic nephropathy identified by bioinformatics analysis. Biomed. Pharmacother. 83, 92–99 (2016).

    Article  CAS  PubMed  Google Scholar 

  278. Argyropoulos, C. et al. Urinary microRNA profiling predicts the development of microalbuminuria in patients with type 1 diabetes. J. Clin. Med. 4, 1498–1517 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  279. Sun, S.-Q. et al. Circulating microRNA-188, -30a, and -30e as early biomarkers for contrast-induced acute kidney injury. J. Am. Heart Assoc. 5, e004138 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  280. Zou, Y.-F. et al. Urinary microRNA-30c-5p and microRNA-192-5p as potential biomarkers of ischemia-reperfusion-induced kidney injury. Exp. Biol. Med. 242, 657–667 (2017).

    Article  CAS  Google Scholar 

  281. Aguado-Fraile, E. et al. A pilot study identifying a set of microRNAs as precise diagnostic biomarkers of acute kidney injury. PLoS One 10, e0127175 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  282. Gaede, L. et al. Plasma microRNA-21 for the early prediction of acute kidney injury in patients undergoing major cardiac surgery. Nephrol. Dial. Transplant. 31, 760–766 (2016).

    Article  CAS  PubMed  Google Scholar 

  283. Huo, R. et al. Predictive value of miRNA-29a and miRNA-10a-5p for 28-day mortality in patients with sepsis-induced acute kidney injury [Chinese]. Nan Fang. Yi Ke Da Xue Xue Bao 37, 646–651 (2017).

    CAS  PubMed  Google Scholar 

  284. Liu, Z. et al. Discovery and validation of miR-452 as an effective biomarker for acute kidney injury in sepsis. Theranostics 10, 11963–11975 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  285. Liu, X. et al. Targeted degradation of the oncogenic microRNA 17-92 cluster by structure-targeting ligands. J. Am. Chem. Soc. 142, 6970–6982 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  286. Reid, G. et al. Clinical development of TargomiRs, a miRNA mimic-based treatment for patients with recurrent thoracic cancer. Epigenomics 8, 1079–1085 (2016).

    Article  CAS  PubMed  Google Scholar 

  287. Lee, E. C. et al. Discovery and preclinical evaluation of anti-miR-17 oligonucleotide RGLS4326 for the treatment of polycystic kidney disease. Nat. Commun. 10, 4148 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  288. Liang, S. et al. Urinary sediment miRNAs reflect tubulointerstitial damage and therapeutic response in IgA nephropathy. BMC Nephrol. 18, 63 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  289. Du, J. et al. MicroRNA-21 and risk of severe acute kidney injury and poor outcomes after adult cardiac surgery. PLoS One 8, e63390 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  290. Zang, J., Maxwell, A. P., Simpson, D. A. & McKay, G. J. Differential expression of urinary exosomal microRNAs miR-21-5p and miR-30b-5p in individuals with diabetic kidney disease. Sci. Rep. 9, 10900 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  291. Chien, H.-Y., Chen, C.-Y., Chiu, Y.-H., Lin, Y.-C. & Li, W.-C. Differential microRNA profiles predict diabetic nephropathy progression in Taiwan. Int. J. Med. Sci. 13, 457–465 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  292. Nakhjavani, M. et al. Plasma levels of miR-21, miR-150, miR-423 in patients with lupus nephritis. Iran. J. Kidney Dis. 13, 198–206 (2019).

    PubMed  Google Scholar 

  293. Assmann, T. S. et al. Circulating miRNAs in diabetic kidney disease: case-control study and in silico analyses. Acta Diabetol. 56, 55–65 (2019).

    Article  CAS  PubMed  Google Scholar 

  294. Pezzolesi, M. G. et al. Circulating TGF-β1-regulated miRNAs and the risk of rapid progression to ESRD in type 1 diabetes. Diabetes 64, 3285–3293 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  295. Tangtanatakul, P. et al. Down-regulation of let-7a and miR-21 in urine exosomes from lupus nephritis patients during disease flare. Asian Pac. J. Allergy Immunol. 37, 189–197 (2019).

    CAS  PubMed  Google Scholar 

  296. Arvin, P. et al. Early detection of cardiac surgery‑associated acute kidney injury by microRNA-21. Bratisl. Lek. Listy 118, 626–631 (2017).

    CAS  PubMed  Google Scholar 

  297. Gholaminejad, A., Abdul Tehrani, H. & Gholami Fesharaki, M. Identification of candidate microRNA biomarkers in diabetic nephropathy: a meta-analysis of profiling studies. J. Nephrol. 31, 813–831 (2018).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

N.M., O.L. and P.L.T. acknowledge funding from the Institut National de Santé et de la Recherche Médicale (INSERM). P.L.T. received research grants from the Fondation pour la Recherche Médicale (FRM, VALID project) and Agence Nationale de la Recherche (ANR, PROTECT-Fi). D.A. received research grants from the BIOMARGIN and ROCKET studies. The BIOMARGIN study is funded by the Seventh Framework Programme (FP7) of the European Commission, in the HEALTH.2012.1.4-1 theme of “innovative approaches to solid organ transplantation” (grant agreement no. 305499). The ROCKET study is funded by the ERAcoSysMed network (H2020 funding framework; grant reference no. JTC2_29).

Author information

Authors and Affiliations

Authors

Contributions

All authors researched data for the article, contributed substantially to discussion of the content, wrote the article and reviewed and/or edited the manuscript before submission.

Corresponding authors

Correspondence to Olivia Lenoir or Pierre-Louis Tharaux.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Nephrology thanks Debora Cerqueira, Jacqueline Ho and the other, anonymous, reviewers for their contribution to the peer review of this work.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Glossary

miR-30 family

miRNA genes are categorized into families based on the mature miRNA sequence and/or the structure of the pre-miRNAs. The miR-30 family is composed of miR-30a, miR-30b, miR-30c-1, miR-30c-2, miR-30d and miR-30e, which are encoded by six genes located on human chromosomes 1, 6 and 8. They share common 5′ sequences but different compensatory sequences near the 3′ end that enable each family member to target different genes.

Polycistronic transcription unit

A transcriptional unit that contains multiple genes with a single promoter that initiates their transcription and regulates their expression.

miRNA sponge

Competitive inhibitors of miRNAs that contain binding sites that are specific to the seed region of the target miRNA, enabling the sponge to block binding of the entire family of related miRNAs.

Agomir

Double-stranded small RNA that can regulate the biological function of target genes by mimicking endogenous miRNA.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mahtal, N., Lenoir, O., Tinel, C. et al. MicroRNAs in kidney injury and disease. Nat Rev Nephrol 18, 643–662 (2022). https://doi.org/10.1038/s41581-022-00608-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41581-022-00608-6

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing