Activin A-Smad Signaling Mediates Connective Tissue Growth Factor Synthesis in Liver Progenitor Cells.
Activin A-Smad Signaling Mediates Connective Tissue Growth Factor Synthesis in Liver Progenitor Cells.
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激活素 A-Smad 信号传导介导肝祖细胞中结缔组织生长因子的合成
DOI：
10.3390/ijms17030408
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发表时间：
2016-03-22
影响因子：
5.6
通讯作者：
Chen XP
中科院分区：
文献类型：
--
作者：
Ding ZY;Jin GN;Wang W;Sun YM;Chen WX;Chen L;Liang HF;Datta PK;Zhang MZ;Zhang B;Chen XP
肝祖细胞（LPCs）在慢性肝损伤中被激活，并可能导致肝纤维化。我们以前的研究报道，LPCs产生结缔组织生长因子（CTGF/CCN 2），肝纤维化的诱导剂，但CTGF/CCN 2在LPCs的生产的调节机制仍然是难以捉摸的。在这项研究中，我们报告，激活素A是一种诱导剂CTGF/CCN 2的LPC。在此，我们发现，激活素A和CTGF/CCN 2的表达均上调，并且激活素A的表达与肝组织中CTGF/CCN 2的表达呈正相关。我们继续显示激活素A在LPC细胞系LE/6和WB-F344中诱导CTGF/CCN 2的从头合成。此外，激活素A通过激活Smad信号传导途径促进肝祖细胞（LPC）中CTGF/CCN 2的自主产生。Smad 2、3和4都是诱导所必需的。总的来说，这些结果为肝中LPC的纤维化作用提供了证据，并表明LPC中的激活素A-Smad-CTGF/CCN 2信号传导可能是肝纤维化的治疗靶点。
Liver progenitor cells (LPCs) are activated in chronic liver damage and may contribute to liver fibrosis. Our previous investigation reported that LPCs produced connective tissue growth factor (CTGF/CCN2), an inducer of liver fibrosis, yet the regulatory mechanism of the production of CTGF/CCN2 in LPCs remains elusive. In this study, we report that Activin A is an inducer of CTGF/CCN2 in LPCs. Here we show that expression of both Activin A and CTGF/CCN2 were upregulated in the cirrhotic liver, and the expression of Activin A positively correlates with that of CTGF/CCN2 in liver tissues. We go on to show that Activin A induced de novo synthesis of CTGF/CCN2 in LPC cell lines LE/6 and WB-F344. Furthermore, Activin A contributed to autonomous production of CTGF/CCN2 in liver progenitor cells (LPCs) via activation of the Smad signaling pathway. Smad2, 3 and 4 were all required for this induction. Collectively, these results provide evidence for the fibrotic role of LPCs in the liver and suggest that the Activin A-Smad-CTGF/CCN2 signaling in LPCs may be a therapeutic target of liver fibrosis.