Skip to main content

Advertisement

SpringerLink
Log in

Peptide Regulation of Cell Differentiation

  • Published:
Stem Cell Reviews and Reports Aims and scope Submit manuscript

Abstract

Short peptides are molecules with small molecular weight, capable of penetrating the cell membrane and nuclear membrane for epigenetic regulation of gene expression, including the genes responsible for cell differentiation. The direction of cell differentiation induction depends on the peptide structure and concentration. AEDG and AEDP peptides induce differentiation of pluripotent cells in the epidermis, mesenchyme and nervous tissue. Peptides KE, AED, KED, AEDG and AAAAEKAAAAEKAAAAEK activate neural differentiation. Peptides AEDL and KEDW induce lung and pancreatic cell differentiation. Differentiation of immune cells is stimulated by KE, DS, (Nα-(γ-E)-E), K(Н-E-OH)-OH, AED, KED, EDA, and KEDG peptides. IRW, GRGDS and YCWSQYLCY peptides activate osteogenic differentiation of stem cells. KE, AEDL, and AEDG peptides also induce plant cells differentiation. Short peptides can take part in activation of the signaling pathways regulating expression of differentiation genes. They can interact with histones changing the availability of genes for transcription, regulate gene methylation and activate or inhibit their expression, as well as directly interact with the DNA. Research in the area of directed stem cell differentiation by peptide regulation is of special importance for developing innovative approaches to molecular medicine and cell therapy.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Paldi, A. (2018). Conceptual challenges of the systemic approach in understanding cell differentiation. Methods in Molecular Biology, 1702, 27–39. https://doi.org/10.1007/978-1-4939-7456-6_3.

    Article  PubMed  Google Scholar 

  2. Choi, S. W., Lee, J. Y., & Kang, K. S. (2017). miRNAs in stem cell aging and age-related disease. Mechanism of Ageing and Development, 168, 20–29. https://doi.org/10.1016/j.mad.2017.08.013.

    Article  CAS  Google Scholar 

  3. López-León, M., Outeiro, T. F., & Goya, R. G. (2017). Cell reprogramming: therapeutic potential and the promise of rejuvenation for the aging brain. Ageing Research Reviews, 40, 168–181. https://doi.org/10.1016/j.arr.2017.09.002.

    Article  CAS  PubMed  Google Scholar 

  4. Xie, Y., Wang, S., Yuan, Q., & Xie, N. (2019). Advances in the research and application of cell penetrating peptides. Sheng Wu Gong Cheng Xue Bao, 35(7), 1162–1173. https://doi.org/10.13345/j.cjb.190030.

    Article  PubMed  Google Scholar 

  5. Khavinson, V. K., Tarnovskaya, S. I., Linkova, N. S., et al. (2013). Short cell-penetrating peptides: a model of interactions with gene promoter site. Bulletin of Experimental Biology and Medicine, 154(3), 403–408. https://doi.org/10.1007/s10517-013-1961-3.

    Article  CAS  PubMed  Google Scholar 

  6. Linkova, N. S., Polyakova, V. O., Trofimov, A. V., et al. (2011). Peptidergic regulation of thymocyte differentiation, proliferation, and apoptosis during aging of the thymus. Bulletin of Experimental Biology and Medicine, 151(2), 239–242. https://doi.org/10.1007/s10517-011-1298-8.

    Article  CAS  Google Scholar 

  7. Khavinson, V. K., Polyakova, V. O., Linkova, N. S., et al. (2011). Peptides regulate cortical thymocytes differentiation, proliferation, and apoptosis. Journal of Amino Acids, 2011(517137), 1–5. https://doi.org/10.4061/2011/517137.

    Article  CAS  Google Scholar 

  8. Khavinson, V. K., Pronyaeva, V. E., Linkova, N. S., & Trofimova, S. V. (2013). Peptidergic regulation of differentiation of embryonic retinal cells. Bulletin of Experimental Biology and Medicine, 1, 172–175. https://doi.org/10.1007/s10517-013-2104-6.

    Article  CAS  Google Scholar 

  9. Linkova, N. S., Trofimov, A. V., & Dudkov, A. V. (2011). Peptides from the pituitary gland and cortex stimulate differentiation of polypotent embryonic tissue. Bulletin of Experimental Biology and Medicine, 151(4), 530–531. https://doi.org/10.1007/s10517-011-1373-1.

    Article  CAS  Google Scholar 

  10. Caputi, S., Trubiani, O., Sinjari, B., Trofimova, S., Diomede, F., Linkova, N., Diatlova, A., & Khavinson, V. (2019). Effect of short peptides on neuronal differentiation of stem cells. International Journal of Immunopathology and Pharmacology, 33, 2058738419828613. https://doi.org/10.1177/2058738419828613.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Sinjari, B., Diomede, F., Khavinson, V., Mironova, E., Linkova, N., Trofimova, S., Trubiani, O., & Caputi, S. (2019). Short peptides protect oral stem cells from ageing. Stem Cell Reviews and Reports, 1–8. https://doi.org/10.1007/s12015-019-09921-3.

  12. Khavinson, V., Linkova, N., Kukanova, E., et al. (2017). Neuroprotective effect of EDR peptide in mouse model of Huntington’s disease. Journal of Neurology and Neuroscience, 8(166), 1–11.

    Google Scholar 

  13. Kraskovskaya, N. A., Kukanova, E. O., Linkova, N. S., et al. (2017). Tripeptides restore the number of neuronal spines under conditions of In Vitro modeled Alzheimer’s disease. Bulletin of Experimental Biology and Medicine, 163(4), 550–553. https://doi.org/10.1007/s10517-017-3882-z.

    Article  CAS  PubMed  Google Scholar 

  14. Khavinson, V. K., Razumovsky, M., Trofimova, S., et al. (2002). Pineal-regulating tetrapeptide epitalon improves eye retina condition in retinitis pigmentosa. Neuroendocrinology Letters, 23(4), 365–368.

    CAS  PubMed  Google Scholar 

  15. Khavinson, V., Trofimova, S., Trofimov, A., & Solomin, I. (2019). Molecular-physiological aspects of regulatory effects of peptide retinaprotectors. Stem Cell Reviews and Reports, 15, 439–442. https://doi.org/10.1007/s12015-019-09882-7.

    Article  CAS  Google Scholar 

  16. Tan, B. T., Wang, L., Li, S., Long, Z. Y., Wu, Y. M., & Liu, Y. (2015). Retinoic acid induced the differentiation of neural stem cells from embryonic spinal cord into functional neurons in vitro. International Journal of Clinical and Experimental Pathology, 8, 8129–8135.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Janesick, A., Wu, S. C., & Blumberg, B. (2015). Retinoic acid signaling and neuronal differentiation. Cellular and Molecular Life Sciences, 72, 1559–1576. https://doi.org/10.1007/s00018-014-1815-9.

    Article  CAS  PubMed  Google Scholar 

  18. Engberg, N., Kahn, M., Petersen, D. R., et al. (2010). Retinoic acid synthesis promotes development of neural progenitors from mouse embryonic stem cells by suppressing endogenous, Wnt-dependent nodal signaling. Stem Cells, 28, 1498–1509. https://doi.org/10.1002/stem.479.

    Article  CAS  PubMed  Google Scholar 

  19. Wu, H., Zhao, J., Fu, B., Yin, S., Song, C., Zhang, J., Zhao, S., & Zhang, Y. (2017). Retinoic acid-induced upregulation of mir-219 promotes the differentiation of embryonic stem cells into neural cells. Cell Death & Disease, 8, e2953. https://doi.org/10.1038/cddis.2017.336.

    Article  CAS  Google Scholar 

  20. Rochette-Egly, C. (2015). Retinoic acid signaling and mouse embryonic stem cell differentiation: Cross talk between genomic and non-genomic effects of RA. Biochimica et Biophysica Acta, 1851, 66–75. https://doi.org/10.1016/j.bbalip.2014.04.003.

    Article  CAS  PubMed  Google Scholar 

  21. Yu, S., Levi, L., Siegel, R., & Noy, N. (2012). Retinoic acid induces neurogenesis by activating both retinoic acid receptors (RARs) and peroxisome proliferator-activated receptor β/δ (PPARβ/δ). The Journal of Biological Chemistry, 287, 42195–42205. https://doi.org/10.1074/jbc.M112.410381.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ma, W., Jin, G. W., Gehret, P. M., et al. (2018). A novel cell penetrating peptide for the differentiation of human neural stem cells. Biomolecules, 8(3), 48. Published 2018 Jul 9. https://doi.org/10.3390/biom8030048.

    Article  CAS  PubMed Central  Google Scholar 

  23. Khavinson, V. K., Tendler, S. M., Vanyushin, B. F., et al. (2014). Peptide regulation of gene expression and protein synthesis in bronchial epithelium. Lung, 192(5), 781–791. https://doi.org/10.1007/s00408-014-9620-7.

    Article  CAS  PubMed  Google Scholar 

  24. Ashapkin, V. V., Linkova, N. S., Khavinson, V. K., & Vanyushin, B. F. (2015). Epigenetic mechanisms of peptidergic regulation of gene expression during aging of human cells. Biochemistry (Mosc), 80(3), 310–322. https://doi.org/10.1134/S0006297915030062.

    Article  CAS  Google Scholar 

  25. Khavinson, V. K., Tendler, S. M., Kasyanenko, N. A., et al. (2015). Tetrapeptide KEDW interacts with DNA and regulates gene expression. American Journal of Biomedical Sciences, 7(3), 156–169. https://doi.org/10.5099/aj150300156.

    Article  CAS  Google Scholar 

  26. Khavinson, V. K., Durnova, A. O., Polyakova, V. O., et al. (2013). Effects of pancragen on the differentiation of pancreatic cells during their ageing. Bulletin of Experimental Biology and Medicine, 154(4), 501–504. https://doi.org/10.1007/s10517-013-1987-6.

    Article  CAS  PubMed  Google Scholar 

  27. Khavinson, V. K., Linkova, N. S., Trofimov, A. V., et al. (2011). Morphofunctional fundamentals for peptide regulation of aging. Biology Bulletin Reviews, 1(4), 389–393.

    Article  Google Scholar 

  28. Sevostianova, N. N., Linkova, N. S., Polyakova, V. O., Chervyakova, N. A., Kostylev, A. V., Durnova, A. O., Kvetnoy, I. M., Abdulragimov, R. I., & Khavinson, V. H. (2013). Immunomodulating effects of Vilon and its analogue in the culture of human and animal thymus cells. Bulletin of Experimental Biology and Medicine, 154(4), 562–565. https://doi.org/10.1007/s10517-013-2000-0.

    Article  CAS  PubMed  Google Scholar 

  29. Otsuki, Y., Ii, M., Moriwaki, K., Okada, M., Ueda, K., & Asahi, M. (2018). W9 peptide enhanced osteogenic differentiation of human adipose-derived stem cells. Biochemical and Biophysical Research Communications, 495(1), 904–910. https://doi.org/10.1016/j.bbrc.2017.11.056.

    Article  CAS  PubMed  Google Scholar 

  30. Furuya, Y., Inagaki, A., Khan, M., et al. (2013). Stimulation of bone formation in cortical bone of mice treated with a receptor activator of nuclear factor-kappaB ligand (RANKL)-binding peptide that possesses osteoclasto- genesis inhibitory activity. The Journal of Biological Chemistry, 288, 5562e5571. https://doi.org/10.1074/jbc.M112.426080.

    Article  CAS  Google Scholar 

  31. Yao, C., Slamovich, E. B., & Webster, T. J. (2008). Enhanced osteoblast functions on anodized titanium with nanotube-like structures. Journal of Biomedical Materials Research. Part A, 85(1), 157–166. https://doi.org/10.1002/jbm.a.31551.

    Article  CAS  PubMed  Google Scholar 

  32. Kim, G. H., Kim, L. S., Park, S. W., et al. (2016). Evaluation of osteoblast-like cell viability and differentiation on the Gly-Arg-Gly-Asp-Ser peptide immobilized titanium dioxide nanotube via chemical grafting. Journal of Nanoscience and Nanotechnology, 16(2), 1396–1399. https://doi.org/10.1166/jnn.2016.11916.

    Article  CAS  PubMed  Google Scholar 

  33. Majumder, K., Chakrabarti, S., Morton, J. S., Panahi, S., Kaufman, S., Davidge, S. T., & Wu, J. (2013). Egg-derived tri-peptide IRW exerts antihypertensive effects in spontaneously hypertensive rats. PLoS One, 8(2013), e82829. https://doi.org/10.1371/journal.pone.0082829.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Huang, W., Chakrabarti, S., Majumder, K., et al. (2010). Egg-derived peptide IRW inhibits TNF-α-induced inflammatory response and oxidative stress in endothelial cells. Journal of Agricultural and Food Chemistry, 58, 10840–10846. https://doi.org/10.1021/jf102120c.

    Article  CAS  PubMed  Google Scholar 

  35. Liao, W., Chakrabarti, S., Davidge, S. T., & Wu, J. (2016). Modulatory effects of egg white ovotransferrin-derived tripeptide IRW (Ile-Arg-Trp) on vascular smooth muscle cells against angiotensin II stimulation. Journal of Agricultural and Food Chemistry, 64, 7342–7347. https://doi.org/10.1021/acs.jafc.6b03513.

    Article  CAS  PubMed  Google Scholar 

  36. Croes, M., Kruyt, M., Loozen, L., et al. (2017). Local induction of inflammation affects bone formation. European Cells & Materials, 33, 211–226. https://doi.org/10.22203/eCM.v033a16.

    Article  CAS  Google Scholar 

  37. Domazetovic, V., Marcucci, G., Iantomasi, T., et al. (2017). Oxidative stress in bone remodeling: role of antioxidants. Clinical Cases in Mineral and Bone Metabolism, 14, 209–216. https://doi.org/10.11138/ccmbm/2017.14.1.209.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Simonet, W. S., Lacey, D. L., Dunstan, C. R., Kelley, M., Chang, M. S., Lüthy, R., Nguyen, H. Q., Wooden, S., Bennett, L., Boone, T., Shimamoto, G., DeRose, M., Elliott, R., Colombero, A., Tan, H. L., Trail, G., Sullivan, J., Davy, E., Bucay, N., Renshaw-Gegg, L., Hughes, T. M., Hill, D., Pattison, W., Campbell, P., Sander, S., van, G., Tarpley, J., Derby, P., Lee, R., & Boyle, W. J. (1997). Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell., 89(2), 309–319. https://doi.org/10.1016/s0092-8674(00)80209-3.

    Article  CAS  PubMed  Google Scholar 

  39. Shang, N., Bhullar, K. S., Hubbard, B. P., & Wu, J. (2019). Tripeptide IRW initiates differentiation in osteoblasts via the RUNX2 pathway. Biochimica et Biophysica Acta (BBA) - General Subjects. https://doi.org/10.1016/j.bbagen.2019.04.007.

    Article  CAS  Google Scholar 

  40. Fedoreyeva, L. I., Dilovarova, T. A., Ashapkin, V. V., Martirosyan, Y. T., Khavinson, V. K., Kharchenko, P. N., & Vanyushin, B. F. (2017). Short exogenous peptides regulate expression of CLE, KNOX1, and GRF family genes in Nikotiana tabacum. Biochemistry (Mosc), 82(4), 521–528. https://doi.org/10.1134/S0006297917040149.

    Article  CAS  Google Scholar 

  41. Anisimov, V. N., & Khavinson, V. K. (2010). Peptide bioregulation of aging: results and prospects. Biogerontology., 11, 139–149. https://doi.org/10.1007/s10522-009-9249-8.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biogerontology, Saint Petersburg Institute of Bioregulation and Gerontology, St. Petersburg, Russia

    Vladimir Khavinson, Natalia Linkova, Anastasiia Diatlova & Svetlana Trofimova

  2. Department of Geriatrics, Propaedeutics and Nursing Management, Mechnikov North-Western State Medical University, St. Petersburg, Russia

    Vladimir Khavinson

  3. Group of Peptide Regulation of Ageing, Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg, Russia

    Vladimir Khavinson

  4. Department of Therapy, Geriatrics, and Anti-Aging Medicine, Academy of Postgraduate Education, Moscow, Russia

    Natalia Linkova & Svetlana Trofimova

Authors
  1. Vladimir Khavinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Natalia Linkova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anastasiia Diatlova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Svetlana Trofimova
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Natalia Linkova.

Ethics declarations

Conflict of Interest

The authors declare no conflict of interest.

Additional information

Publisher’s Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khavinson, V., Linkova, N., Diatlova, A. et al. Peptide Regulation of Cell Differentiation. Stem Cell Rev and Rep 16, 118–125 (2020). https://doi.org/10.1007/s12015-019-09938-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12015-019-09938-8

Keywords

Search

Navigation