Transforming growth factor 0i (TGF-,) enhances the cell surface binding of 1251-fibronectin by cultured human fibroblasts. The effect of TGF-4 on cell surface binding was maximal after 2 h of exposure to TFG-0 and did not require epidermal growth factor or protein synthesis. The enhancement was dose dependent and was found with the '25I-labeled 70-kilodalton amino-terminal fragment of fibronectin as well as with '251-fibronectin. Treatment of cultures with TGF-0 for 6 h resulted in a threefold increase in the estimated number of fibronectin binding sites. The increase in number of binding sites was accompanied by an increased accumulation of labeled fibronectin in detergent-insoluble extracellular matrix. The effect of TGF-j was biphasic; after 6 h of exposure, less labeled fibronectin bound to treated cultures than to control cultures.Exposure of cells to TGF-0 for >6 h caused a two-to threefold increase in the accumulation of cellular fibronectin in culture medium as detected by a quantitative enzyme-linked immunosorbent assay. The second phase of the biphasic effect and the increase in soluble cellular fibronectin were blocked by cycloheximide. Immunofluorescence staining of fibroblast cultures with antifibronectin revealed that TGF-I caused a striking increase in fibronectin fibrils. The 70-kilodalton amino-terminal fragment of fibronectin, which blocks incorporation of fibronectin into extracellular matrix, blocked anchorage-independent growth of NRK-49F cells in the presence of epidermal growth factor. Our results show that an increase in the binding and rate of assembly of exogenous fibronectin is an early event preceding the increase in expression of extracellular matrix proteins. Such an early increase in cell surface binding of exogenous fibronectin may be a mechanism whereby TGF-0 can modify extracellular matrix characteristics rapidly after tissue injury or during embryonic morphogenesis.The presence of high concentrations of transforming growth factor i (TGF-P) in platelets (3) has led to speculation about the role of this factor in wound healing. Repair of tissue injury requires formation of a provisional extracellular matrix, as well as cell migration and cell division (14,20). An increased accumulation of protein, including collagen, was observed in Buffalo rats when TGF-P and epidermal growth factor (EGF) were injected into implanted Schilling-Hunt chambers (42). Subcutaneous injection of newborn mice with TGF-P causes formation of granulation tissue at the site of injection (38). TGF-P also increases the healing rate and wound strength of incisional wounds in rats (29). These in vivo findings are supported by in vitro studies which show that human dermal fibroblasts as well as NRK-49F cells incorporate more proline or leucine into collagen after exposure to TGF-P (38). Ignotz and Massague (17) showed that TGF-P increases the synthesis of fibronectin and collagen in a wide variety of normal and transformed cells and that it increases the incorporation of fibronectin and collagen into the extrac...
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