Skip to main content
Log in

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

  • Mechanisms of Normal and Pathological Tissue Development
  • Published:
Russian Journal of Developmental Biology Aims and scope Submit manuscript

Abstract

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.

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

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cicha, I. and Goppelt-Struebe, M., Connective tissue growth factor: context-dependent functions and mechanisms of regulation, Biofactors, 2009, vol. 35, pp. 200–208.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    CAS  Google Scholar 

  • 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.

    CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Kubota, S. and Takigawa, M., CCN family proteins and angiogenesis: from embryo to adulthood, Angiogenesis, 2007, vol. 10, pp. 1–11.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    CAS  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to O. V. Vasilieva.

Additional information

Original Russian Text © O.V. Vasilieva, N.N. Golubtzova, F.N. Filippov, A.G. Gunin, 2016, published in Ontogenez, 2016, Vol. 47, No. 2, pp. 75–82.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vasilieva, O.V., Golubtzova, N.N., Filippov, F.N. et al. Connective tissue growth factor (CTGF) in the human dermis through ontogenesis. Russ J Dev Biol 47, 63–68 (2016). https://doi.org/10.1134/S1062360416020089

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1062360416020089

Keywords

Navigation