Skip to main content
SpringerLink
Log in

Age-related changes of angiomotin and endostatin content in human skin

  • Published:
Advances in Gerontology Aims and scope Submit manuscript

Abstract

Angiomotin- and endostatin-positive structures were studied by the indirect immunohistochemical method in the skin of human fetuses that died antenatally from different causes in the 20th to 40th weeks of pregnancy and in skin samples extracted during the autopsy of humans who died from different causes at ages from 1 day to 85 years. The cells of epidermis, the fibroblasts, sweat and sebaceous glands of the dermis, and the blood vessels had a positive reaction to angiomotin and endostatin. Considering the fundamental importance of angiomotin and endostatin for angiogenesis, we studied the content of these substances in the blood vessels. Angiomotin-positive blood vessels were detected in skin samples of humans of all ages. An agedependent decrease was found in the angiomotin content in blood vessels of the dermis; it was more strongly expressed in humans aged 61–85 years. Endostatin-positive blood vessels were detected in the skin samples of humans of all ages. An age-dependent increase in the endostatin content in blood vessels of the dermis was found. The change in the angiomotin and endostatin contents and the balance between these substances probably have a negative effect on the angiogenesis processes in human skin during aging.

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

Similar content being viewed by others

References

  1. Gunin, A.G., Petrov, V.V., Vasilieva, O.V., and Golubtsova, N.N., Age-related changes of blood vessels in the human dermis, Adv. Gerontol., 2015, vol. 5, no. 2, pp. 65–71.

    Article  Google Scholar 

  2. Aase, K., Ernkvist, M., Ebarasi, L., et al., Angiomotin regulates endothelial cell migration during embryonic angiogenesis, Genes Dev., 2007, vol. 21, pp. 2055–2068.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Baluk, P. and McDonald, D.M., Markers for microscopic imaging of lymphangiogenesis and angiogenesis, Ann. N.Y. Acad. Sci., 2008, vol. 1131, pp. 1–12.

    Article  PubMed  Google Scholar 

  4. Boosani, C.S. and Sudhakar, Y.A., Proteolytically derived endogenous angioinhibitors on riginating from the extracellular matrix, Pharmaceuticals (Basel), 2011, vol. 4, pp. 1551–1577.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bratt, A., Birot, O., Sinha, I., et al., Angiomotin regulates endothelial cell-cell junctions and cell motility, J. Biol. Chem., 2005, vol. 280, no. 41, pp. 34859–34869.

    Article  CAS  PubMed  Google Scholar 

  6. Dai, X., She, P., Chi, F., et al., Phosphorylation of angiomotin by Lats1/2 kinases inhibits F-actin binding, cell migration, and angiogenesis, J. Biol. Chem., 2013, vol. 288, pp. 34041–34051.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Dhanabal, M., Ramchandran, R., Waterman, M.J., et al., Endostatin induces endothelial cell apoptosis, J. Biol. Chem., 1999, vol. 274, pp. 11721–11726.

    Article  CAS  PubMed  Google Scholar 

  8. Dhanabal, M., Volk, R., Ramchandran, R., et al., Cloning, expression, and in vitro activity of human endostatin, Biochem. Biophys. Res. Commun., 1999, vol. 258, pp. 345–352.

    Article  CAS  PubMed  Google Scholar 

  9. Ernkvist, M., Luna Persson, N., Audebert, S., et al., The Amot/Patj/Syx signaling complex spatially controls RhoA GTPase activity in migrating endothelial cells, Blood, 2009, vol. 113, no. 1, pp. 244–253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Fang, J., Shing, Y., Wiederschain, D., et al., Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotype in a tumor model, Proc. Natl. Acad. Sci. U.S.A., 2000, vol. 97, pp. 3884–3889.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Gunin, A.G., Petrov, V.V., Golubtzova, N.N., et al., Age-related changes in angiogenesis in human dermis, Exp. Gerontol., 2014, vol. 55, pp. 143–151.

    Article  CAS  PubMed  Google Scholar 

  12. Hong, W., Angiomotin’g YAP into the nucleus for cell proliferation and cancer development, Sci. Signal., 2013, vol. 291, no. 6, p. pe27. doi 10.1126/scisignal. 2004573

    Google Scholar 

  13. Huang, Y., Shi, H., Zhou, H., et al., The angiogenic function of nucleolin is mediated by vascular endothelial growth factor and nonmuscle myosin, Blood, 2006, vol. 107, pp. 3564–3571.

    Article  CAS  PubMed  Google Scholar 

  14. Itoh, Y., Ito, A., Iwata, K., et al., Plasma membranebound tissue inhibitor of metalloproteinases (TIMP)-2 specifically inhibits matrix metalloproteinase 2 (gelatinase a) activated on the cell surface, J. Biol. Chem., 1998, vol. 273, pp. 24360–24367.

    Article  CAS  PubMed  Google Scholar 

  15. Jones, E.A, Noble, F., and Eichmann, A., What determines blood vessel structure? Genetic prespecification vs. hemodynamics, Physiology (Bethesda), 2006, vol. 21, pp. 388–395.

    Article  PubMed  Google Scholar 

  16. Kim, J.H. and Jung, M., Adipose-derived stem cells as a new therapeutic modality for ageing skin, Exp. Dermatol., 2011, vol. 20, pp. 383–387.

    Article  CAS  PubMed  Google Scholar 

  17. Kim, Y.M., Jang, J.W., Lee, O.H., et al., Endostatin inhibits endothelial and tumor cellular invasion by blocking the activation and catalytic activity of matrix metalloproteinase, Cancer Res., 2000, vol. 60, pp. 5410–5413.

    CAS  PubMed  Google Scholar 

  18. Lee, J.H. and Yoo, J.H., Knockdown of moesin expression accelerates cellular senescence of human dermal microvascular endothelial cells, Yonsei Med. J., 2010, vol. 51, pp. 438–447.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Moleirinho, S., Guerrant, W., and Kissil, J.L., The angiomotins—from discovery to function, FEBS Lett., 2014, vol. 588, pp. 2693–2703.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. O’Reilly, M.S., Boehm, T., Shing, Y., et al., Endostatin: an endogenous inhibitor of angiogenesis and tumor growth, Cell, 1997, vol. 88, pp. 277–285.

    Article  PubMed  Google Scholar 

  21. Risau, W., Mechanisms of angiogenesis, Nature, 1997, vol. 386, pp. 671–674.

    Article  CAS  PubMed  Google Scholar 

  22. Shi, H., Huang, Y., Zhou, H., et al., Nucleolin is a receptor that mediates antiangiogenic and antitumor activity of endostatin, Blood, 2007, vol. 110, pp. 2899–2906.

    Article  CAS  PubMed  Google Scholar 

  23. Starke, R.D. and Ferraro, F., Endothelial von Willebrand factor regulates angiogenesis, Blood, 2011, vol. 117, pp. 1071–1080.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Sudhakar, A., Sugimoto, H., Yang, C., et al., Human tumstatin and human endostatin exhibit distinct antiangiogenic activities mediated by aVß3 and a5ß1 integrins, Proc. Natl. Acad. Sci. U.S.A., 2003, vol. 100, pp. 4766–4771.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Troyanovsky, B., Levchenko, T., Månsson, G., et al., Angiomotin: an angiostatin binding protein that regulates endothelial cell migration and tube formation, J. Cell Biol., 2001, vol. 152, pp. 1247–1254.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zaidi, M., Krolikowki, J.G., Jones, D.W., et al., Transient repetitive exposure to low level light therapy enhances collateral blood vessel growth in the ischemic hindlimb of the tight skin mouse, Photochem. Photobiol., 2013, vol. 89, pp. 709–713.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zhang, H., Wang, Z., Peng, Q., et al., Tumor refractoriness to endostatin anti-angiogenesis is associated with the recruitment of CD11b+Gr1+ myeloid cells and inflammatory cytokines, Tumori, 2013, vol. 99, pp. 723–733.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Chuvash State University, Moskovskii pr. 15, Cheboksary, 428015, Russia

    N. N. Golubtsova, O. V. Vasilieva, V. V. Petrov, F. N. Filippov & A. G. Gunin

Authors
  1. N. N. Golubtsova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. O. V. Vasilieva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. V. Petrov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F. N. Filippov
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. G. Gunin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N. N. Golubtsova.

Additional information

Original Russian Text © N.N. Golubtsova, O.V. Vasilieva, V.V. Petrov, F.N. Filippov, A.G. Gunin, 2015, published in Uspekhi Gerontologii, 2015, Vol. 28, No. 4, pp. 762–768.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Golubtsova, N.N., Vasilieva, O.V., Petrov, V.V. et al. Age-related changes of angiomotin and endostatin content in human skin. Adv Gerontol 6, 153–159 (2016). https://doi.org/10.1134/S2079057016020065

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S2079057016020065

Keywords

Search

Navigation