Transcriptional activation of transforming growth factor β1 and its receptors by the Kruppel-like factor Zf9/core promoter-binding protein and Sp1 -: Potential mechanisms for autocrine fibrogenesis in response to injury
Transcriptional activation of transforming growth factor β1 and its receptors by the Kruppel-like factor Zf9/core promoter-binding protein and Sp1 -: Potential mechanisms for autocrine fibrogenesis in response to injury
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DOI：
10.1074/jbc.273.50.33750
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发表时间：
1998-12-11
影响因子：
4.8
通讯作者：
Friedman, SL
中科院分区：
文献类型：
--
作者：
Kim, Y;Ratziu, V;Friedman, SL
我们通过研究Zf9/核心启动子结合蛋白（一种在肝星状细胞（HSC）活化早期诱导的Kruppel样锌指转录因子）与I型和II型TGF-β 1和TGF-β受体启动子的相互作用，探索了组织修复中转化生长因子β（TGF-β）活性的调节。通过电泳迁移率变动分析，培养激活的HSC的核提取物与TGF-β 1启动子内的两个串联GC盒强烈结合，但与单个GC盒的结合最少;这些结果与Zf9对TGF-β 1启动子-报告子的反式激活相关，Zf9在原代HSC、HSC-T6细胞、（SV 40永生化大鼠RSC系）、Hep G2细胞或果蝇施奈德（S2）细胞。重组Zf9-GST还结合I型和II型TGF-β受体启动子内的GC盒序列。I型和II型TGF-β受体启动子在哺乳动物细胞中也被Zf9反式激活，但在S2细胞中没有。相反，Spl显著反式激活S2细胞中的两个受体启动子。这些结果表明：（a）Zf 9/核心启动子结合蛋白可能通过反式激活TGF-β 1基因及其关键信号受体来增强TGF-β活性，（B）Zf 9和Sp1对TGF-β 1及其受体启动子的反式激活潜力并不相同，取决于细胞环境。
We have explored the regulation of transforming growth factor beta (TGF-beta) activity in tissue repair by examining the interactions of Zf9/core promoter-binding protein, a Kruppel-like zinc finger transcription factor induced early in hepatic stellate cell (HSC) activation, with promoters for TGF-beta 1 and TGF-beta receptors, types I and II. Nuclear extracts from culture-activated HSCs bound avidly by electrophoretic mobility shift assay to two tandem GC boxes within the TGF-beta 1 promoter but minimally to a single GC box; these results correlated with transactivation by Zf9 of TGF-beta 1 promoter-reporters, Zf9 transactivated the full-length TGF-beta 1 promoter in either primary HSCs, HSC-T6 cells (an SV40-immortalized rat RSC line), Hep G2 cells, or Drosophila Schneider (S2) cells. Recombinant Zf9-GST also bound to GC box sequences within the promoters for the types I and II TGF-beta receptors. Both type I and type II TGF-beta receptor promoters were also transactivated by Zf9 in mammalian cells but not in S2 cells. In contrast, Spl significantly transactivated both receptor promoters in S2 cells. These results suggest that (a) Zf9/core promoterbinding protein may enhance TGF-beta activity through transactivation of both the TGF-beta 1 gene and its key signaling receptors, and (b) transactivating potential of Zf9 and Sp1 toward promoters for TGF-beta 1 and its recep tors are not identical and depend on the cellular context.