Transforming growth factor-β (TGF-β) type I and type II receptors are both required for TGF-β-mediated extracellular matrix production in lung fibroblasts
Transforming growth factor-β (TGF-β) type I and type II receptors are both required for TGF-β-mediated extracellular matrix production in lung fibroblasts
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DOI：
10.1016/s0303-7207(99)00021-0
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发表时间：
1999-04-25
影响因子：
4.1
通讯作者：
Zhao, Y
中科院分区：
文献类型：
--
作者：
Zhao, Y
转化生长因子- β (tgf - β)调节多种细胞活动，包括细胞生长、分化和细胞外基质的产生。tgf - β I型和II型丝氨酸/苏氨酸激酶受体（T β RI和T β RII）已被确定为tgf - β受体的信号转导。本研究旨在研究I型和II型受体在tgf - β诱导的肺成纤维细胞细胞外基质生成中的作用。我们构建了含有缺少细胞质丝氨酸/苏氨酸激酶结构域的T β RI和T β RII截断衍生物（T β RI Delta K和T X RII Delta K）的表达质粒，并将其转染到肺成纤维细胞中。肺成纤维细胞表达的T β RII δ K能够结合i -125- tgf - β 1，而单独表达的T β RI δ K则不能结合配体。tgf - β 1与T β RI δ k的结合和交联需要go与T β RII的表达。当使用tgf - β 1处理时，肺成纤维细胞上调张力蛋白和纤维连接蛋白的产生。T β RI和T β RII的激酶缺陷缺失是tgf - β信号转导的主要抑制剂。单独表达T β - RI - δ K或T β - RII - δ K足以阻断tgf - β诱导的肺成纤维细胞张力蛋白和纤维连接蛋白的产生。结果表明，T β RI和T β RII是tgf - β信号在肺成纤维细胞细胞外基质生成调控中所必需的。1999爱思唯尔科学爱尔兰有限公司版权所有。
Transforming growth factor-beta (TGF-beta) regulates a variety of cellular activities including cell growth, differentiation and extracellular matrix production. The TGF-beta type I and type II serine/threonine kinase receptors (T beta RI and T beta RII) have been identified as signal-transducing TGF-beta receptors. This study was undertaken to examine the role of the type I and type II receptors in TGF-beta-induced extracellular matrix production of lung fibroblasts. We constructed expression plasmids containing truncated derivatives of T beta RI and T beta RII that lacked the cytoplasmic serine/threonine kinase domain (T beta RI Delta K and T X RII Delta K), and transfected them into lung fibroblasts. T beta RII Delta K expressed by lung fibroblasts was able to bind I-125-TGF-beta 1, whereas T beta RI Delta K was unable to bind ligand when expressed alone. Go-expression with T beta RII was required for binding and cross-linking of TGF-beta 1 to T beta RI Delta K. Lung fibroblasts upregulate tenascin and fibronectin production when treated with TGF-beta 1 The kinase-defective deletions of both T beta RI and T beta RII were dominant-acting inhibitors of TGF-beta signal transduction. Expression of either T beta RI Delta K or T beta RII Delta K alone was sufficient to block TGF-beta-induced tenascin and fibronectin production of lung fibroblasts. The results indicate that both T beta RI and T beta RII were required for TGF-beta signaling in regulation of extracellular matrix production by lung fibroblasts. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.