Ignotz R A, Massagué J
J Biol Chem. 1986 Mar 25;261(9):4337-45.
We have examined whether the extracellular matrix is a biochemical target for transforming growth factor-beta (TGFbeta). We find that TGFbeta increases the expression of the major extracellular matrix proteins, fibronectin and collagen. This effect is a general response to TGFbeta seen in primary cultures and established lines of cells from various types, normal and transformed. The relative incorporation of fibronectin and collagen into the matrix also increases in response to TGFbeta. The effect of TGFbeta on fibronectin levels as characterized in chick embryo fibroblasts is rapid, selective, persistent, and specific, and involves transcriptional events; it is not mimicked by other growth factors tested. The induction of anchorage-independent growth of normal fibroblasts by TGFbeta is mimicked by fibronectin and is specifically blocked by inhibitors of fibronectin binding to its cell surface receptor. The results demonstrate a functional involvement of fibronectin in mediating cellular responses to TGFbeta, and suggest a model for TGFbeta action based on the control of the extracellular matrix in target cells.
我们研究了细胞外基质是否是转化生长因子-β（TGFβ）的生化靶点。我们发现TGFβ可增加主要细胞外基质蛋白纤连蛋白和胶原蛋白的表达。这种效应是TGFβ在原代培养物以及来自各种类型（正常和转化）细胞的已建立细胞系中所观察到的普遍反应。纤连蛋白和胶原蛋白相对掺入基质的量也会因TGFβ而增加。TGFβ对鸡胚成纤维细胞中纤连蛋白水平的影响迅速、具有选择性、持久且具有特异性，并且涉及转录事件；其他所测试的生长因子无法模拟这种影响。TGFβ诱导正常成纤维细胞的非贴壁依赖性生长可被纤连蛋白模拟，并且可被纤连蛋白与其细胞表面受体结合的抑制剂特异性阻断。这些结果证明了纤连蛋白在介导细胞对TGFβ反应中的功能性参与，并基于对靶细胞中细胞外基质的控制提出了一个TGFβ作用模型。
