EXTRACELLULAR-MATRIX REGULATES EXPRESSION OF THE TGF-BETA-1 GENE
EXTRACELLULAR-MATRIX REGULATES EXPRESSION OF THE TGF-BETA-1 GENE
复制标题
DOI：
10.1083/jcb.120.1.253
复制
发表时间：
1993-01-01
影响因子：
7.8
通讯作者：
DERYNCK, R
中科院分区：
文献类型：
--
作者：
STREULI, CH;SCHMIDHAUSER, C;DERYNCK, R
转化生长因子-β（TGF-β）是细胞增殖的有效调节剂，并部分通过诱导各种ECM蛋白的合成来调节细胞与其细胞外基质（ECM）的相互作用。TGF-β的三种不同亚型在体内特定细胞群中以确定的模式合成。在特定的情况下，TGF-β 1，这种定义明确的和有限的表达与其合成几乎所有的细胞在culture.Using乳腺上皮细胞作为一个模型系统，我们评估了基质依赖性的TGF-β 1的表达。TGF-β 1的表达水平在塑料上的细胞中很高，但当细胞在重建的基底膜基质上培养时强烈下调。相比之下，在任一基质上的细胞中的TGF-β 2 mRNA水平保持不变。使用氯霉素乙酰转移酶基因作为报告基因的TGF-β 1启动子的控制下，我们表明，从这个启动子的转录被抑制时，细胞与内源性合成或外源性管理的基底膜接触。TGF-β 1启动子活性强烈地由基底膜的缺乏诱导，即，通过细胞与塑料的直接接触。这种从TGF-β 1启动子转录的调节发生在不存在允许完全分化的催乳激素的情况下。因此，我们的研究结果表明，基底膜是一个重要的调节TGF-β 1的合成，并解释了为什么大多数细胞在塑料培养表达TGF-β 1在体内的TGF-β 1的合成更受限制。我们提出，有一个反馈回路，从而TGF-β 1诱导的基底膜成分的合成被抑制，一旦一个功能性的基底膜存在。最后，这些结果与我们目前的知识调节TGF-β 1和TGF-β 2的合成，表明，在体内，TGF-β 1可能发挥重要作用，在调节ECM的合成和细胞-ECM的相互作用，而TGF-β 2可能是更重要的形态发生过程。
Transforming growth factor-beta (TGF-beta) is a potent regulator of cell proliferation and modulates the interactions of cells with their extracellular matrix (ECM), in part by inducing the synthesis of various ECM proteins. Three different isoforms of TGF-beta are synthesized in a defined pattern in specific cell populations in vivo. In the specific case of TGF-beta1, this well-defined and limited expression stands in sharp contrast to its synthesis by virtually all cells in culture.Using mammary epithelial cells as a model system, we evaluated the substratum dependence of the expression of TGF-beta1. The level of TGF-beta1 expression is high in cells on plastic, but is strongly downregulated when cells are cultured on a reconstituted basement membrane matrix. In contrast, TGF-beta2 mRNA levels in cells on either substratum remain unchanged. Using the chloramphenicol acetyl transferase gene as reporter gene under the control of the TGF-beta1 promoter, we show that transcription from this promoter is suppressed when the cells are in contact with either endogenously synthesized or exogenously administered basement membrane. TGF-beta1 promoter activity is strongly induced by the absence of basement membrane, i.e., by direct contact of the cells with plastic. This modulation of transcription from the TGF-beta1 promoter occurs in the absence of lactogenic hormones which allow full differentiation. Our results thus indicate that basement membrane is an important regulator of TGF-beta1 synthesis, and explain why most cells in culture on plastic express TGF-beta1 in contrast with the more restricted TGF-beta1 synthesis in vivo. We propose that there is a feedback loop whereby TGF-beta1-induced synthesis of basement membrane components is repressed once a functional basement membrane is present. Finally, these results together with our current knowledge of regulation of TGF-beta1 and TGF-beta2 synthesis, suggest that, in vivo, TGF-beta1 may play a major role in regulating the ECM synthesis and the cell-ECM interactions, whereas TGF-beta2 may be more important in morphogenetic processes.