TGF-BETA ENHANCES THE PRODUCTION OF HYALURONAN IN HUMAN LUNG BUT NOT IN SKIN FIBROBLASTS

Transforming growth factor-β (TGF-β) enhances the production of extracellular matrix components, such as type I and type III collagen, fibronectin, and proteoglycans, in various cell types. The effect on hyaluronan synthesis in relation to proteoglycan synthesis has not been investigated. Human lung or skin fibroblast cultures were treated with TGF-β in serum-free medium for various periods of time. 35SO4 or [3H]glucosamine was then added to the cultures in the absence of TGF-β for up to 48 h. Hyaluronan and proteoglycans were isolated by ion-exchange chromatography and quantitated. TGF-β induced a three- to fourfold increase in hyaluronan production by lung cells but had no effect on skin fibroblasts. In contrast, proteoglycan synthesis was enhanced in both cell types, although skin fibroblasts responded at lower concentrations of TGF-β. Increased accumulation of hyaluronan was noted only in the cell medium, whereas proteoglycan accumulation was observed both in the medium and in the cell layer. The ED50 for TGF-β on hyaluronan accumulation in lung cells was the same as that for proteoglycan accumulation i.e., 40 pM. In skin fibroblasts the ED50 was considerably lower (4 pM). The induction time needed to attain full effect of TGF-β was 6 h for both hyaluronan and proteoglycan synthesis. These results indicate that TGF-β has tissue-specific effects on matrix production which may be of importance for control of cell proliferation in various disease states. © 1990.