The Role and Relation of VEGF, TGF-beta1 and CTGF in the Scar Formation of the Rat

ABSTRACT

Skin fibrotic disorders are understood to develop under the influence of various cytokines, such as transforming growth factor(TGF)-beta1, connective tissue growth factor(CTGF) and vascular endothelial growth factor (VEGF). To establish an appropriate animal model of skin fibrosis by exogenous application of growth factors, the author investigated the in vivo effects of growth factors by injecting recombinant TGF-beta1 protein and pCMV- Flag5-CTGF into the subcutaneous tissue of Sprague- Dawley rats. A single application of TGF-beta1 protein and CTGF DNA resulted in the formation of transient granulation tissue. Immunohistochemical finding showed increased expression of TGF-beta1 protein after injection of pCMV-Flag5-CTGF. In situ hybridization analysis revealed the expression of CTGF mRNA after injection of TGF-beta1 protein. VEGF expression was not affected by the TGF-beta1 and CTGF injection. These findings suggest TGF-beta1 and CTGF are deeply related with skin fibrosis and it appears that TGF-beta1 may cause the induction of CTGF expression. The animal model on skin fibrosis by exogenous application of TGF-beta1 protein and CTGF DNA developed in this study may be useful for future studies on fibrotic disorders.