Advances in Gerontology

, Volume 9, Issue 3, pp 267–273 | Cite as

Transforming Growth Factor-β (TGF-β) in Human Skin during Aging

  • A. G. GuninEmail author
  • N. N. Golubtzova


The goal of the present study is to examine the level of transforming growth factor-β (TGF-β) in fibroblasts and blood microvessels of the human dermis from the development until deep aging (from 20 weeks’ gestation to 85 years of age), and to determine the role of TGF-β in age-dependent changes in the number of fibroblasts and blood microvessels in the dermis. The contents of TGF-β, proliferating cell nuclear antigen (PCNA), and endothelial cell marker CD31 are assessed with the indirect immunohistochemical technique. The results show an increase in the of the proportion of the fibroblasts stained positive for TGF-β in the dermis from 20 weeks’ gestation until 85 years of age. A greater increase in the percentage of TGF-β positive fibroblasts in the human dermis is observed after birth and after the age of 40 years. The content of TGF-β in the blood microvessels of the human dermis decreases significantly after the age of 41 years. An age-related increase in the proportion of fibroblasts stained positive for TGF-β is associated with an age-related reduction of the total number and the percentage of PCNA positive fibroblasts in the human dermis. An age-related decrease in the content of TGF-β in blood microvessels is accompanied by an age-related decrease in their number in the dermis. An age-related increase in the fibroblast content of TGF-β is associated with an age-dependent decrease in their total number and proliferation in the dermis. The age-related reduction of TGF-β content in blood microvessels of dermis is associated with an age-related decrease in the number of blood microvessels in the dermis.


aging skin fibroblasts blood vessels TGF-β CD31 PCNA 



This work was supported by RFBR and Chuvash Republic (16-44-210018, 18-44-210001).


The authors declare that they have no conflict of interest. The study was approved by the Ethics Committee of the Medical faculty of Ulianov Chuvash State University.


  1. 1.
    Gunin, A.G. and Golubtsova, N.N., Thyroid hormone receptors in human skin during aging, Adv. Gerontol., 2018, vol. 8, no. 3, pp. 216–223.CrossRefGoogle Scholar
  2. 2.
    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.CrossRefGoogle Scholar
  3. 3.
    Fritz, P., Hones, J., Lutz, D., et al., Quantitative immunohistochemistry: standardization and possible application in research and surgical pathology, Acta Histochem., 1989, vol. 37, suppl., pp. 213–219.Google Scholar
  4. 4.
    Gunin, A.G., Kornilova, N.K., Vasilieva, O.V., and Petrov, V.V., Age-related changes in proliferation, the numbers of mast cells, eosinophils, CD45 positive cells in human dermis, J. Gerontol., Ser. A, 2011, vol. 66, pp. 385–392.Google Scholar
  5. 5.
    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.CrossRefGoogle Scholar
  6. 6.
    Haque, S. and Morris, J.C., Transforming growth factor-β: a therapeutic target for cancer, Hum. Vaccines Immunother., 2017, vol. 13, pp. 1741–1750.CrossRefGoogle Scholar
  7. 7.
    Kawamura, H., Nakatsuka, R., Matsuoka, Y., et al., TGF-β signaling accelerates senescence of human bone-derived CD271 and SSEA-4 double-positive mesenchymal stromal cells, Stem Cell Rep., 2018, vol. 10, pp. 920–932.CrossRefGoogle Scholar
  8. 8.
    Qin, Z., Xia, W., Fisher, G.J., Voorhees, J.J., and Quan, T., YAP/TAZ regulates TGF-β/Smad3 signaling by induction of Smad7 via AP-1 in human skin dermal fibroblasts, Cell. Commun. Signaling, 2018, vol. 16, p. 18.CrossRefGoogle Scholar
  9. 9.
    Rizzardi, A.E., Johnson, A.T., Vogel, R.I., et al., Quantitative comparison of immunohistochemical staining measured by digital image analysis versus pathologist visual scoring, Diagn. Pathol., 2012, vol. 7, p. 42.CrossRefGoogle Scholar
  10. 10.
    Seidal, T., Balaton, A.J., and Battifora, H., Interpretation and quantification of immunostains, Am. J. Surg. Pathol., 2001, vol. 25, pp. 1204–1207.CrossRefGoogle Scholar
  11. 11.
    Wang, A.S. and Dreesen, O., Biomarkers of cellular senescence and skin aging, Front. Genet., 2018, vol. 9, p. 247.CrossRefGoogle Scholar
  12. 12.
    Wang, Z., Perez, M., Lee, E.S., Kojima, S., et al., The functional relationship between transglutaminase 2 and transforming growth factor-β1 in the regulation of angiogenesis and endothelialmesenchymal transition, Cell Death Dis., 2017, vol. 8, p. e3032.CrossRefGoogle Scholar
  13. 13.
    Wei, W. and Ji, S., Cellular senescence: molecular mechanisms and pathogenicity, J. Cell Physiol., 2018.
  14. 14.
    Zonneville, J., Safina, A., Truskinovsky, A.M., et al., TGF-β signaling promotes tumor vasculature by enhancing the pericyteendothelium association, BMC Cancer, 2018, vol. 18, p. 670.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2019

Authors and Affiliations

  1. 1.Chuvash State UniversityCheboksaryRussia

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