Synergistic enhancement of type I and III collagen production in cultured fibroblasts by transforming growth factor-beta and ascorbate.

Transforming growth factor-beta (TGF-beta) is a prototype of a family of polypeptides that regulates cellular growth and phenotypic differentiation [(1986) Science 233, 532-534; (1987) Cell 49, 437-438]. TGF-beta injection induces angiogenesis and fibrosis locally [(1986) Proc. Natl. Acad. Sci. USA 83, 4167-4171; (1987) Science 237, 1333-1336] and stimulates the synthesis of extracellular matrix proteins, fibronectin, collagens, and proteoglycans in vitro in many cell types [(1986) J. Biol. Chem. 261, 4337-4345; (1987) Biochem J. 247, 597-604]. Ascorbate is also known to induce collagen synthesis and to promote wound healing [(1988) J. Invest. Dermatol. 90, 420-424; (1986) Coll. Rel. Res. 6, 455-466]. We report that in cultured human skin fibroblasts, ascorbate and TGF-beta synergistically enhance the biosynthesis of type I and III collagens and their steady-state mRNAs. TGF-beta alone has no enhancing effect on type III collagen synthesis. The cooperation between ascorbate and TGF-beta may be of significance in wound healing and in disorders of fibrosis.