REGULATION OF CONNECTIVE-TISSUE GROWTH-FACTOR GENE-EXPRESSION IN HUMAN SKIN FIBROBLASTS AND DURING WOUND REPAIR

Connective tissue growth factor (CTGF) is a cysteine-rich peptide that exhibits platelet-derived growth factor (PDGF)-like biological and im munological activities. CTGF is a member of a family of peptides that include serum-induced immediate early gene products, a v-src-induced p eptide, and a putative avian transforming gene, nov. In the present st udy, we demonstrate that human foreskin fibroblasts produce high level s of CTGF mRNA and protein after activation with transforming growth f actor beta (TGF-beta) but not other growth factors including PDGF, epi dermal growth factor, and basic fibroblast growth factor. Because of t he high level selective induction of CTGF by TGF-beta, it appears that CTGF is a major autocrine growth factor produced by TGF-beta-treated human skin fibroblasts. Cycloheximide did not block the large TGF-beta stimulation of CTGF gene expression, indicating that it is directly r egulated by TGF-beta. Similar regulatory mechanisms appear to function in vivo during wound repair where there is a coordinate expression of TGF-beta1 before CTGF in regenerating tissue, suggesting a cascade pr ocess for control of tissue regeneration and repair.