Russian Journal of Developmental Biology

, Volume 47, Issue 2, pp 63–68 | Cite as

Connective tissue growth factor (CTGF) in the human dermis through ontogenesis

  • O. V. Vasilieva
  • N. N. Golubtzova
  • F. N. Filippov
  • A. G. Gunin
Mechanisms of Normal and Pathological Tissue Development


Connective tissue growth factor (CTGF) was examined in the structures of dermis of humans with different ages, from 20 weeks of pregnancy to 85 years. By immunohistochemistry, the fibroblasts and blood vessels positively stained for CTGF were observed in the dermis of all examined ages. An age-dependent increase in the percent of the fibroblasts and blood vessels positively stained for CTGF in the dermis was observed. A statistically significant negative correlation was found between the age-dependent changes in the total number of fibroblasts, percent of the fibroblasts with positive staining for proliferating cell nuclear antigen, and portion of the fibroblasts with positive staining for CTGF. Another statistically significant negative correlation was found between the age-dependent changes in the number of blood vessels and portion of the blood vessels with a positive staining for CTGF. The results suggest that CTGF has an inhibitory influence on the angiogenesis and fibroblast renewal in the human dermis through ontogenesis.


dermis ontogenesis fibroblasts blood vessels connective tissue growth factor 


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  1. Abraham, D., Connective tissue growth factor: growth factor, matricellular organizer, fibrotic biomarker or molecular target for anti-fibrotic therapy in SSc?, Rheumatology (Oxford), 2008, vol. 47, suppl. 5, pp. v8–v9.CrossRefGoogle Scholar
  2. Chen, Y., Abraham, D.J., Shi-Wen, X., et al., CCN2 (connective tissue growth factor) promotes fibroblast adhesion to fibronectin, Mol. Biol. Cell, 2004, vol. 15, pp. 5635–5646.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Chen, S., McLean, S., Carter, D.E., et al., The gene expression profile induced by Wnt 3a in NIH 3T3 fibroblasts, J. Cell. Commun. Signal., 2007, vol. 1, pp. 175–183.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Chen, C.C. and Lau, L.F., Functions and mechanisms of action of CCN matricellular proteins, Int. J. Biochem. Cell. Biol., 2009, vol. 41, pp. 771–783.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Cicha, I. and Goppelt-Struebe, M., Connective tissue growth factor: context-dependent functions and mechanisms of regulation, Biofactors, 2009, vol. 35, pp. 200–208.CrossRefPubMedGoogle Scholar
  6. Colwell, A.S., Krummel, T.M., Longaker, M.T., et al., Fetal and adult fibroblasts have similar TGF-betamediated, Smad-dependent signaling pathways, Plast. Reconstr. Surg., 2006, vol. 117, pp. 2277–2283.CrossRefPubMedGoogle Scholar
  7. Dammeier, J., Beer, H.D., Brauchle, M., et al., Dexamethasone is a novel potent inducer of connective tissue growth factor expression. Implications for glucocorticoid therapy, J. Biol. Chem., 1998, vol. 273, pp. 18185–18190.CrossRefPubMedGoogle Scholar
  8. Du, J., Klein, J.D., Hassounah, F., et al., Aging increases ccn1 expression leading to muscle senescence, Am. J. Physiol. Cell. Physiol., 2014, vol. 306, pp. C28–C36.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Gao, R. and Brigstock, D.R., Connective tissue growth factor (CCN2)induces adhesion of rat activated hepatic stellate cells by binding of its C-terminal domain to integrin alpha(v)beta(3) and heparan sulfate proteoglycan, J. Biol. Chem., 2004, vol. 279, pp. 8848–8855.CrossRefPubMedGoogle Scholar
  10. Gunin, A.G., Kornilova, N.K., Petrov, V.V., et al., Age changes in the number and proliferation of fibroblasts in the human skin, Adv. Genontol., 2011, vol. 3, no. 4, pp. 299–303.CrossRefGoogle Scholar
  11. Gunin, A.G., Petrov, V.V., Golubtzova, N.N., et al., Agerelated changes in angiogenesis in human dermis, Exp. Gerontol., 2014, vol. 55, pp. 143–151.CrossRefPubMedGoogle Scholar
  12. Gunin, A.G., Petrov, V.V., Vasilyeva, O.V., et al., Agerelated changes of blood vessels in the human dermis, Adv. Geronotol., 2015, vol. 5, no. 2, pp. 65–71.CrossRefGoogle Scholar
  13. Hall-Glenn, F., De Young, R.A., Huang, B.L., et al., CCN2/connective tissue growth factor is essential for pericyte adhesion and endothelial basement membrane formation during angiogenesis, Adv. Geronotol., 2012, vol. 7, p. e30562.Google Scholar
  14. Inoki, I., Shiomi, T., Hashimoto, G., et al., Connective tissue growth factor binds vascular endothelial growth factor (VEGF) and inhibits VEGF-induced angiogenesis, FASEB J., 2002, vol. 16, pp. 219–221.PubMedGoogle Scholar
  15. Kapoor, M., Liu, S., Huh, K., et al., Connective tissue growth factor promoter activity in normal and wounded skin, Fibrogenesis Tissue Repair, 2008, vol. 1, p. 3.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Kim, K.H., Park, G.T., Lim, Y.B., et al., Expression of connective tissue growth factor, a biomarker in senescence of human diploid fibroblasts, is up-regulated by a transforming growth factor-beta-mediated signaling pathway, Biochem. Biophys. Res. Commun., 2004, vol. 318, pp. 819–825.CrossRefPubMedGoogle Scholar
  17. Kubota, S. and Takigawa, M., CCN family proteins and angiogenesis: from embryo to adulthood, Angiogenesis, 2007, vol. 10, pp. 1–11.CrossRefPubMedGoogle Scholar
  18. Markiewicz, M., Nakerakanti, S.S., Kapanadze, B., et al., Connective tissue growth factor (CTGF/CCN2) mediates angiogenic effect of S1P in human dermal microvascular endothelial cells, Microcirculation, 2011, vol. 18, pp. 1–11.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Nishida, T., Kubota, S., Fukunaga, T., et al., CTGF/Hcs24, hypertrophic chondrocyte-specific gene product, interacts with perlecan in regulating the proliferation and differentiation of chondrocytes, Russ. J. Dev. Biol., 2003, vol. 196, pp. 265–275.Google Scholar
  20. Petrov, V.V., Vasilyeva, O.V., Kornilova, N.K., et al., Agerelated changes in mast cells and eosinophils of human dermis, Russ. J. Dev. Biol., 2013, vol. 44, no. 3, pp. 139–143.CrossRefGoogle Scholar
  21. Quan, T., He, T., Kang, S., et al., Connective tissue growth factor: expression in human skin in vivo and inhibition by ultraviolet irradiation, J. Invest. Dermatol., 2002, vol. 118, pp. 402–408.CrossRefPubMedGoogle Scholar
  22. Safadi, F.F., Xu, J., Smock, S.L., et al., Expression of connective tissue growth factor in bone: its role in osteoblast proliferation and differentiation in vitro and bone formation in vivo, J. Cell Physiol., 2003, vol. 196, pp. 51–62.CrossRefPubMedGoogle Scholar
  23. Shi-Wen, X., Leask, A., and Abraham, D., Regulation and function of connective tissue growth factor/CCN2 in tissue repair, scarring and fibrosis, Cytokine Growth Factor Rev., 2008, vol. 19, pp. 133–144.CrossRefPubMedGoogle Scholar
  24. Smerdel-Ramoya, A., Zanotti, S., Stadmeyer, L., et al., Skeletal overexpression of connective tissue growth factor (ctgf) impairs bone formation and causes osteopenia, Endocrinology, 2008, vol. 149, pp. 4374–4381.CrossRefPubMedPubMedCentralGoogle Scholar
  25. Suzuma, K., Naruse, K., Suzuma, I., et al., Vascular endothelial growth factor induces expression of connective tissue growth factor via KDR, Flt1, and phosphatidylinositol 3-kinase-akt-dependent pathways in retinal vascular cells, J. Biol. Chem., 2000, vol. 275, pp. 40725–40731.CrossRefPubMedGoogle Scholar

Copyright information

© Pleiades Publishing, Inc. 2016

Authors and Affiliations

  • O. V. Vasilieva
    • 1
  • N. N. Golubtzova
    • 1
  • F. N. Filippov
    • 1
  • A. G. Gunin
    • 1
  1. 1.Chuvash State UniversityCheboksaryRussia

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