Skip to main content

Advertisement

Log in

MicroRNAs and Diabetic Complications

  • Published:
Journal of Cardiovascular Translational Research Aims and scope Submit manuscript

Abstract

Both Type 1 and Type 2 diabetes can lead to debilitating microvascular complications such as retinopathy, nephropathy and neuropathy, as well as macrovascular complications such as cardiovascular diseases including atherosclerosis and hypertension. Diabetic complications have been attributed to several contributing factors such as hyperglycemia, hyperlipidemia, advanced glycation end products, growth factors, and inflammatory cytokines/chemokines. However, current therapies are not fully efficacious and hence there is an imperative need for a better understanding of the molecular mechanisms underlying diabetic complications in order to identify newer therapeutic targets. microRNAs (miRNAs) are short non-coding RNAs that repress target gene expression via post-transcriptional mechanisms. Emerging evidence shows that they have diverse cellular and biological functions and play key roles in several diseases. In this review, we explore the role of miRNAs in the pathology of diabetic complications and also discuss the potential use of miRNAs as novel diagnostic and therapeutic targets for diabetic complications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. He, Z., & King, G. L. (2004). Microvascular complications of diabetes. Endocrinology and Metabolism Clinics of North America, 33, 215–238. xi-xii.

    Article  PubMed  CAS  Google Scholar 

  2. Beckman, J. A., Creager, M. A., & Libby, P. (2002). Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. JAMA, 287, 2570–2581.

    Article  PubMed  CAS  Google Scholar 

  3. Brownlee, M. (2005). The pathobiology of diabetic complications: a unifying mechanism. Diabetes, 54, 1615–1625.

    Article  PubMed  CAS  Google Scholar 

  4. King, G. L., Kunisaki, M., Nishio, Y., Inoguchi, T., Shiba, T., & Xia, P. (1996). Biochemical and molecular mechanisms in the development of diabetic vascular complications. Diabetes, 45(Suppl 3), S105–S108.

    PubMed  CAS  Google Scholar 

  5. Villeneuve, L. M., Reddy, M. A., & Natarajan, R. (2011). Epigenetics: deciphering its role in diabetes and its chronic complications. Clinical and Experimental Pharmacology and Physiology, 38, 401–409.

    Article  PubMed  CAS  Google Scholar 

  6. Cooper, M. E., & El-Osta, A. (2010). Epigenetics: mechanisms and implications for diabetic complications. Circulation Research, 107, 1403–1413.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  8. Bartel, D. P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116, 281–297.

    Article  PubMed  CAS  Google Scholar 

  9. Bartel, D. P. (2009). MicroRNAs: target recognition and regulatory functions. Cell, 136, 215–233.

    Article  PubMed  CAS  Google Scholar 

  10. Croce, C. M. (2009). Causes and consequences of microRNA dysregulation in cancer. Nature Reviews Genetics, 10, 704–714.

    Article  PubMed  CAS  Google Scholar 

  11. He, L., & Hannon, G. J. (2004). MicroRNAs: small RNAs with a big role in gene regulation. Nature Reviews Genetics, 5, 522–531.

    Article  PubMed  CAS  Google Scholar 

  12. Zamore, P. D., & Haley, B. (2005). Ribo-gnome: the big world of small RNAs. Science, 309, 1519–1524.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  14. Wightman, B., Ha, I., & Ruvkun, G. (1993). Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell, 75, 855–862.

    Article  PubMed  CAS  Google Scholar 

  15. Filipowicz, W., Bhattacharyya, S. N., & Sonenberg, N. (2008). Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nature Reviews Genetics, 9, 102–114.

    Article  PubMed  CAS  Google Scholar 

  16. Stefani, G., & Slack, F. J. (2008). Small non-coding RNAs in animal development. Nature Reviews Molecular Cell Biology, 9, 219–230.

    Article  PubMed  CAS  Google Scholar 

  17. Kim, V. N. (2005). MicroRNA biogenesis: coordinated cropping and dicing. Nature Reviews Molecular Cell Biology, 6, 376–385.

    Article  PubMed  CAS  Google Scholar 

  18. Small, E. M., & Olson, E. N. (2011). Pervasive roles of microRNAs in cardiovascular biology. Nature, 469, 336–342.

    Article  PubMed  CAS  Google Scholar 

  19. Bhatt, K., Mi, Q. S., & Dong, Z. (2011). microRNAs in kidneys: biogenesis, regulation, and pathophysiological roles. American Journal of Physiology. Renal Physiology, 300, F602–F610.

    Article  PubMed  CAS  Google Scholar 

  20. Fernandez-Valverde, S. L., Taft, R. J., & Mattick, J. S. (2011). MicroRNAs in beta-cell biology, insulin resistance, diabetes and its complications. Diabetes, 60, 1825–1831.

    Article  PubMed  CAS  Google Scholar 

  21. Kato, M., Arce, L., & Natarajan, R. (2009). MicroRNAs and their role in progressive kidney diseases. Clinical Journal of the American Society of Nephrology, 4, 1255–1266.

    Article  PubMed  CAS  Google Scholar 

  22. Zhang, C. (2010). MicroRNAs in vascular biology and vascular disease. Journal of Cardiovascular Translational Research, 3, 235–240.

    Article  PubMed  CAS  Google Scholar 

  23. Kempen, J. H., O’Colmain, B. J., Leske, M. C., Haffner, S. M., Klein, R., Moss, S. E., et al. (2004). The prevalence of diabetic retinopathy among adults in the United States. Archives of Ophthalmology, 122, 552–563.

    Article  PubMed  Google Scholar 

  24. Saaddine, J. B., Honeycutt, A. A., Narayan, K. M., Zhang, X., Klein, R., & Boyle, J. P. (2008). Projection of diabetic retinopathy and other major eye diseases among people with diabetes mellitus: United States, 2005–2050. Archives of Ophthalmology, 126, 1740–1747.

    Article  PubMed  Google Scholar 

  25. Kovacs, B., Lumayag, S., Cowan, C., & Xu, S. (2011). MicroRNAs in early diabetic retinopathy in streptozotocin-induced diabetic rats. Investigative Ophthalmology & Visual Science, 52, 4402–4409.

    Article  CAS  Google Scholar 

  26. Feng, B., Chen, S., McArthur, K., Wu, Y., Sen, S., Ding, Q., et al. (2011). miR-146a-Mediated extracellular matrix protein production in chronic diabetes complications. Diabetes, 60, 2975–2984.

    Article  PubMed  CAS  Google Scholar 

  27. McArthur, K., Feng, B., Wu, Y., Chen, S., & Chakrabarti, S. (2011). MicroRNA-200b regulates vascular endothelial growth factor-mediated alterations in diabetic retinopathy. Diabetes, 60, 1314–1323.

    Article  PubMed  CAS  Google Scholar 

  28. Silva, V. A., Polesskaya, A., Sousa, T. A., Correa, V. M., Andre, N. D., Reis, R. I., et al. (2011). Expression and cellular localization of microRNA-29b and RAX, an activator of the RNA-dependent protein kinase (PKR), in the retina of streptozotocin-induced diabetic rats. Molecular Vision, 17, 2228–2240.

    PubMed  CAS  Google Scholar 

  29. Kato, M., Park, J. T., & Natarajan, R. (2012) MicroRNAs and the glomerulus. Experimental Cell Research, 318, 993–1000.

    Google Scholar 

  30. Ziyadeh, F. N., & Sharma, K. (2003). Overview: combating diabetic nephropathy. Journal of the American Society of Nephrology, 14, 1355–1357.

    Article  PubMed  Google Scholar 

  31. Kato, M., Zhang, J., Wang, M., Lanting, L., Yuan, H., Rossi, J. J., et al. (2007). MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors. Proceedings of the National Academy of Sciences of the United States of America, 104, 3432–3437.

    Article  PubMed  CAS  Google Scholar 

  32. Sharma, K., & Ziyadeh, F. N. (1995). Hyperglycemia and diabetic kidney disease. The case for transforming growth factor-beta as a key mediator. Diabetes, 44, 1139–1146.

    Article  PubMed  CAS  Google Scholar 

  33. Yamamoto, T., Nakamura, T., Noble, N. A., Ruoslahti, E., & Border, W. A. (1993). Expression of transforming growth factor beta is elevated in human and experimental diabetic nephropathy. Proceedings of the National Academy of Sciences of the United States of America, 90, 1814–1818.

    Article  PubMed  CAS  Google Scholar 

  34. Kato, M., Wang, L., Putta, S., Wang, M., Yuan, H., Sun, G., et al. (2010). Post-transcriptional up-regulation of Tsc-22 by Ybx1, a target of miR-216a, mediates TGF-{beta}-induced collagen expression in kidney cells. Journal of Biological Chemistry, 285, 34004–34015.

    Article  PubMed  CAS  Google Scholar 

  35. Kato, M., Arce, L., Wang, M., Putta, S., Lanting, L., & Natarajan, R. (2011). A microRNA circuit mediates transforming growth factor-beta1 autoregulation in renal glomerular mesangial cells. Kidney International, 80, 358–368.

    Article  PubMed  CAS  Google Scholar 

  36. Kato, M., Putta, S., Wang, M., Yuan, H., Lanting, L., Nair, I., et al. (2009). TGF-beta activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTEN. Nature Cell Biology, 11, 881–889.

    Article  PubMed  CAS  Google Scholar 

  37. Kato, M., & Natarajan, R. (2009). microRNA cascade in diabetic kidney disease: big impact initiated by a small RNA. Cell Cycle, 8, 3613–3614.

    Article  PubMed  CAS  Google Scholar 

  38. Wang, Q., Wang, Y., Minto, A. W., Wang, J., Shi, Q., Li, X., et al. (2008). MicroRNA-377 is up-regulated and can lead to increased fibronectin production in diabetic nephropathy. The FASEB Journal, 22, 4126–4135.

    Article  CAS  Google Scholar 

  39. Wang, X. X., Jiang, T., Shen, Y., Caldas, Y., Miyazaki-Anzai, S., Santamaria, H., et al. (2010). Diabetic nephropathy is accelerated by farnesoid X receptor deficiency and inhibited by farnesoid X receptor activation in a type 1 diabetes model. Diabetes, 59, 2916–2927.

    Article  PubMed  CAS  Google Scholar 

  40. Long, J., Wang, Y., Wang, W., Chang, B. H., & Danesh, F. R. (2010). Identification of microRNA-93 as a novel regulator of vascular endothelial growth factor in hyperglycemic conditions. Journal of Biological Chemistry, 285, 23457–23465.

    Article  PubMed  CAS  Google Scholar 

  41. Long, J., Wang, Y., Wang, W., Chang, B. H., & Danesh, F. R. (2011). MicroRNA-29c is a signature microRNA under high glucose conditions that targets Sprouty homolog 1, and its in vivo knockdown prevents progression of diabetic nephropathy. Journal of Biological Chemistry, 286, 11837–11848.

    Article  PubMed  CAS  Google Scholar 

  42. Wang, B., Komers, R., Carew, R., Winbanks, C. E., Xu, B., Herman-Edelstein, M., et al. (2012). Suppression of microRNA-29 expression by TGF-beta1 promotes collagen expression and renal fibrosis. Journal of the American Society of Nephrology, 23, 252–265.

    Article  PubMed  CAS  Google Scholar 

  43. Krupa, A., Jenkins, R., Luo, D. D., Lewis, A., Phillips, A., & Fraser, D. (2010). Loss of MicroRNA-192 promotes fibrogenesis in diabetic nephropathy. Journal of the American Society of Nephrology, 21, 438–447.

    Article  PubMed  CAS  Google Scholar 

  44. Wang, B., Herman-Edelstein, M., Koh, P., Burns, W., Jandeleit-Dahm, K., Watson, A., et al. (2010). E-cadherin expression is regulated by miR-192/215 by a mechanism that is independent of the profibrotic effects of transforming growth factor-beta. Diabetes, 59, 1794–1802.

    Article  PubMed  CAS  Google Scholar 

  45. Wang, B., Koh, P., Winbanks, C., Coughlan, M. T., McClelland, A., Watson, A., et al. (2011). miR-200a Prevents renal fibrogenesis through repression of TGF-beta2 expression. Diabetes, 60, 280–287.

    Article  PubMed  CAS  Google Scholar 

  46. Dey, N., Das, F., Mariappan, M. M., Mandal, C. C., Ghosh-Choudhury, N., Kasinath, B. S., et al. (2011). MicroRNA-21 orchestrates high glucose-induced signals to TOR complex 1, resulting in renal cell pathology in diabetes. Journal of Biological Chemistry, 286, 25586–25603.

    Article  PubMed  CAS  Google Scholar 

  47. Zhang, Z., Peng, H., Chen, J., Chen, X., Han, F., Xu, X., et al. (2009). MicroRNA-21 protects from mesangial cell proliferation induced by diabetic nephropathy in db/db mice. FEBS Letters, 583, 2009–2014.

    Article  PubMed  CAS  Google Scholar 

  48. Fu, Y., Zhang, Y., Wang, Z., Wang, L., Wei, X., Zhang, B., et al. (2010). Regulation of NADPH oxidase activity is associated with miRNA-25-mediated NOX4 expression in experimental diabetic nephropathy. American Journal of Nephrology, 32, 581–589.

    Article  PubMed  CAS  Google Scholar 

  49. Caporali, A., Meloni, M., Vollenkle, C., Bonci, D., Sala-Newby, G. B., Addis, R., et al. (2010). Deregulation of microRNA-503 contributes to diabetes mellitus-induced impairment of endothelial function and reparative angiogenesis after limb ischemia. Circulation, 123, 282–291.

    Article  Google Scholar 

  50. Natarajan, R., & Nadler, J. L. (2004). Lipid inflammatory mediators in diabetic vascular disease. Arteriosclerosis, Thrombosis, and Vascular Biology, 24, 1542–1548.

    Article  PubMed  CAS  Google Scholar 

  51. Brownlee, M. (2001). Biochemistry and molecular cell biology of diabetic complications. Nature, 414, 813–820.

    Article  PubMed  CAS  Google Scholar 

  52. Devaraj, S., Dasu, M. R., & Jialal, I. (2010). Diabetes is a proinflammatory state: a translational perspective. Expert Review of Endocrinology and Metabolism, 5, 19–28.

    PubMed  CAS  Google Scholar 

  53. Libby, P., Ridker, P. M., & Maseri, A. (2002). Inflammation and atherosclerosis. Circulation, 105, 1135–1143.

    Article  PubMed  CAS  Google Scholar 

  54. Shan, Z. X., Lin, Q. X., Deng, C. Y., Zhu, J. N., Mai, L. P., Liu, J. L., et al. (2010). miR-1/miR-206 regulate Hsp60 expression contributing to glucose-mediated apoptosis in cardiomyocytes. FEBS Letters, 584, 3592–3600.

    Article  PubMed  CAS  Google Scholar 

  55. Katare, R., Caporali, A., Zentilin, L., Avolio, E., Sala-Newby, G., Oikawa, A., et al. (2011). Intravenous gene therapy with PIM-1 via a cardiotropic viral vector halts the progression of diabetic cardiomyopathy through promotion of prosurvival signaling. Circulation Research, 108, 1238–1251.

    Article  PubMed  CAS  Google Scholar 

  56. Wang, X. H., Qian, R. Z., Zhang, W., Chen, S. F., Jin, H. M., & Hu, R. M. (2009). MicroRNA-320 expression in myocardial microvascular endothelial cells and its relationship with insulin-like growth factor-1 in type 2 diabetic rats. Clinical and Experimental Pharmacology and Physiology, 36, 181–188.

    Article  PubMed  Google Scholar 

  57. Care, A., Catalucci, D., Felicetti, F., Bonci, D., Addario, A., Gallo, P., et al. (2007). MicroRNA-133 controls cardiac hypertrophy. Nature Medicine, 13, 613–618.

    Article  PubMed  CAS  Google Scholar 

  58. Feng, B., Chen, S., George, B., Feng, Q., & Chakrabarti, S. (2010). miR133a regulates cardiomyocyte hypertrophy in diabetes. Diabetes/Metabolism Research and Reviews, 26, 40–49.

    Article  PubMed  CAS  Google Scholar 

  59. Shen, E., Diao, X., Wang, X., Chen, R., & Hu, B. (2011). MicroRNAs involved in the mitogen-activated protein kinase cascades pathway during glucose-induced cardiomyocyte hypertrophy. American Journal of Pathology, 179, 639–650.

    Article  PubMed  CAS  Google Scholar 

  60. Greco, S., Fasanaro, P., Castelvecchio, S., D’Alessandra, Y., Arcelli, D., Di Donato, M., et al. (2012). MicroRNA dysregulation in diabetic ischemic heart failure patients. Diabetes (in press).

  61. van Rooij, E., Sutherland, L. B., Liu, N., Williams, A. H., McAnally, J., Gerard, R. D., et al. (2006). A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure. Proceedings of the National Academy of Sciences of the United States of America, 103, 18255–18260.

    Article  PubMed  Google Scholar 

  62. Duisters, R. F., Tijsen, A. J., Schroen, B., Leenders, J. J., Lentink, V., van der Made, I., et al. (2009). miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocardial matrix remodeling. Circulation Research, 104, 170–178. 176p following 178.

    Article  PubMed  CAS  Google Scholar 

  63. Thum, T., Gross, C., Fiedler, J., Fischer, T., Kissler, S., Bussen, M., et al. (2008). MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature, 456, 980–984.

    Article  PubMed  CAS  Google Scholar 

  64. Reddy, M. A., & Natarajan, R. (2011). Epigenetic mechanisms in diabetic vascular complications. Cardiovascular Research, 90, 421–429.

    Article  PubMed  CAS  Google Scholar 

  65. Shanmugam, N., Reddy, M. A., & Natarajan, R. (2008). Distinct roles of heterogeneous nuclear ribonuclear protein K and microRNA-16 in cyclooxygenase-2 RNA stability induced by S100b, a ligand of the receptor for advanced glycation end products. Journal of Biological Chemistry, 283, 36221–36233.

    Article  PubMed  CAS  Google Scholar 

  66. Villeneuve, L. M., Reddy, M. A., Lanting, L. L., Wang, M., Meng, L., & Natarajan, R. (2008). Epigenetic histone H3 lysine 9 methylation in metabolic memory and inflammatory phenotype of vascular smooth muscle cells in diabetes. Proceedings of the National Academy of Sciences of the United States of America, 105, 9047–9052.

    Article  PubMed  CAS  Google Scholar 

  67. Villeneuve, L. M., Kato, M., Reddy, M. A., Wang, M., Lanting, L., & Natarajan, R. (2010). Enhanced levels of microRNA-125b in vascular smooth muscle cells of diabetic db/db mice lead to increased inflammatory gene expression by targeting the histone methyltransferase Suv39h1. Diabetes, 59, 2904–2915.

    Article  PubMed  CAS  Google Scholar 

  68. Reddy, M. A., Jin, W., Villeneuve, L., Wang, M., Lanting, L., Todorov, I., et al. (2012). Pro-inflammatory role of MicroRNA-200 in vascular smooth muscle cells from diabetic mice. Arteriosclerosis, Thrombosis, and Vascular Biology, 32, 721–729.

    Article  PubMed  CAS  Google Scholar 

  69. Jin, W., Reddy, M. A., Chen, Z., Putta, S., Lanting, L., Kato, M., et al. (2012). Small RNA sequencing reveals microRNAs that modulate angiotensin II effects in vascular smooth muscle cells. Journal of Biological Chemistry (in press).

  70. Thomas, M. C., Groop, P. H., & Tryggvason, K. (2012). Towards understanding the inherited susceptibility for nephropathy in diabetes. Current Opinion in Nephrology and Hypertension, 21, 195–202.

    Article  PubMed  CAS  Google Scholar 

  71. Bruno, A. E., Li, L., Kalabus, J. L., Pan, Y., Yu, A., & Hu, Z. (2012). miRdSNP: a database of disease-associated SNPs and microRNA target sites on 3′UTRs of human genes. BMC Genomics, 13, 44.

    Article  PubMed  CAS  Google Scholar 

  72. Sun, G., Yan, J., Noltner, K., Feng, J., Li, H., Sarkis, D. A., et al. (2009). SNPs in human miRNA genes affect biogenesis and function. RNA, 15, 1640–1651.

    Article  PubMed  CAS  Google Scholar 

  73. Miao, F., Chen, Z., Zhang, L., Liu, Z., Wu, X., Yuan, Y. C. et al. (2012). Profiles of epigenetic histone post-translational modifications at type 1 diabetes susceptible genes. Journal of Biological Chemistry (in press).

  74. Sapienza, C., Lee, J., Powell, J., Erinle, O., Yafai, F., Reichert, J., et al. (2011). DNA methylation profiling identifies epigenetic differences between diabetes patients with ESRD and diabetes patients without nephropathy. Epigenetics, 6, 20–28.

    Article  PubMed  CAS  Google Scholar 

  75. Farazi, T. A., Spitzer, J. I., Morozov, P., & Tuschl, T. (2011). miRNAs in human cancer. The Journal of Pathology, 223, 102–115.

    Article  PubMed  CAS  Google Scholar 

  76. Fabbri, M. (2010). miRNAs as molecular biomarkers of cancer. Expert Review of Molecular Diagnostics, 10, 435–444.

    Article  PubMed  CAS  Google Scholar 

  77. Wang, K., Zhang, S., Marzolf, B., Troisch, P., Brightman, A., Hu, Z., et al. (2009). Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proceedings of the National Academy of Sciences of the United States of America, 106, 4402–4407.

    Article  PubMed  CAS  Google Scholar 

  78. Mitchell, P. S., Parkin, R. K., Kroh, E. M., Fritz, B. R., Wyman, S. K., Pogosova-Agadjanyan, E. L., et al. (2008). Circulating microRNAs as stable blood-based markers for cancer detection. Proceedings of the National Academy of Sciences of the United States of America, 105, 10513–10518.

    Article  PubMed  CAS  Google Scholar 

  79. Tijsen, A. J., Creemers, E. E., Moerland, P. D., de Windt, L. J., van der Wal, A. C., Kok, W. E., et al. (2010). MiR423-5p as a circulating biomarker for heart failure. Circulation Research, 106, 1035–1039.

    Article  PubMed  CAS  Google Scholar 

  80. Wang, G., Kwan, B. C., Lai, F. M., Chow, K. M., Kam-Tao Li, P., & Szeto, C. C. (2010). Expression of microRNAs in the urinary sediment of patients with IgA nephropathy. Disease Markers, 28, 79–86.

    PubMed  Google Scholar 

  81. Neal, C. S., Michael, M. Z., Pimlott, L. K., Yong, T. Y., Li, J. Y., & Gleadle, J. M. (2011). Circulating microRNA expression is reduced in chronic kidney disease. Nephrology, Dialysis, Transplantation, 26, 3794–3802.

    Article  PubMed  CAS  Google Scholar 

  82. Starkey Lewis, P. J., Dear, J., Platt, V., Simpson, K. J., Craig, D. G., Antoine, D. J., et al. (2011). Circulating microRNAs as potential markers of human drug-induced liver injury. Hepatology, 54, 1767–1776.

    Article  PubMed  CAS  Google Scholar 

  83. Elmen, J., Lindow, M., Schutz, S., Lawrence, M., Petri, A., Obad, S., et al. (2008). LNA-mediated microRNA silencing in non-human primates. Nature, 452, 896–899.

    Article  PubMed  CAS  Google Scholar 

  84. Krutzfeldt, J., Rajewsky, N., Braich, R., Rajeev, K. G., Tuschl, T., Manoharan, M., et al. (2005). Silencing of microRNAs in vivo with ‘antagomirs’. Nature, 438, 685–689.

    Article  PubMed  Google Scholar 

  85. Putta, S., Lanting, L., Sun, G., Lawson, G., Kato, M., & Natarajan, R. (2012). Inhibiting microRNA-192 ameliorates renal fibrosis in diabetic nephropathy. Journal of the American Society of Nephrology, 23, 458–469.

    Article  PubMed  CAS  Google Scholar 

  86. Sun, L., Zhang, D., Liu, F., Xiang, X., Ling, G., Xiao, L., et al. (2011). Low-dose paclitaxel ameliorates fibrosis in the remnant kidney model by down-regulating miR-192. The Journal of Pathology, 225, 364–377.

    Article  PubMed  CAS  Google Scholar 

  87. Snove, O., Jr., & Rossi, J. J. (2006). Expressing short hairpin RNAs in vivo. Nature Methods, 3, 689–695.

    Article  PubMed  CAS  Google Scholar 

  88. Ebert, M. S., Neilson, J. R., & Sharp, P. A. (2007). MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nature Methods, 4, 721–726.

    Article  PubMed  CAS  Google Scholar 

  89. Chung, A. C., Huang, X. R., Meng, X., & Lan, H. Y. (2010). miR-192 mediates TGF-beta/Smad3-driven renal fibrosis. Journal of the American Society of Nephrology, 21, 1317–1325.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge funding from the National Institutes of Health (NIDDK and NHLBI), the Juvenile Diabetes Research Foundation and the American Diabetes Association.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rama Natarajan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Natarajan, R., Putta, S. & Kato, M. MicroRNAs and Diabetic Complications. J. of Cardiovasc. Trans. Res. 5, 413–422 (2012). https://doi.org/10.1007/s12265-012-9368-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12265-012-9368-5

Keywords

Navigation