TIMP-1 expression induced by IL-32 is mediated through activation of AP-1 signal pathway.
TIMP-1 expression induced by IL-32 is mediated through activation of AP-1 signal pathway.
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DOI：
10.1016/j.intimp.2016.06.002
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发表时间：
2016-09
影响因子：
5.6
通讯作者：
Haixia Xu;Shaoquan Zhang;Xingfei Pan;H. Cao;Xiaoping Huang;Qi-huan Xu;Haizhen A. Zhong;Xiaomou Peng
中科院分区：
文献类型：
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作者：
Haixia Xu;Shaoquan Zhang;Xingfei Pan;H. Cao;Xiaoping Huang;Qi-huan Xu;Haizhen A. Zhong;Xiaomou Peng
肝纤维化是慢性肝病发展为肝硬化甚至肝细胞癌的必经阶段。肝纤维化的特征是细胞外基质（ECM）的进行性积聚。基质金属蛋白酶（MMP）和金属蛋白酶组织抑制剂（TIMP）介导ECM产生和降解之间的平衡。TIMP-1是ECM合成和降解的重要调节因子。IL-32是一种多功能细胞因子，可通过激活AP-1、NF-κβ、p38 MAPK等信号通路诱导IL-1β、IL-6、IL-8等细胞因子的表达。肝纤维化肝组织中IL-32表达增加。然而，IL-32在肝纤维化发病机制中的作用尚不完全清楚。近年来的研究表明，TIMP-1的表达是通过AP-1信号通路的激活来诱导的。因此，本研究检测IL-32对肝星状细胞系LX-2表达TIMP-1的影响。IL-32可诱导LX-2细胞表达TIMP-1，且呈剂量依赖性。IL-32可通过激活AP-1信号通路，提高TIMP-1启动子活性，诱导TIMP-1表达。TIMP-1表达增加可促进LX-2细胞的迁移。结论：IL-32可能通过诱导TIMP-1表达参与肝纤维化的发病机制。
Hepatic fibrosis is a necessarily stage from the progression of chronic liver diseases to cirrhosis, even hepatocellular carcinoma (HCC). Hepatic fibrosis is characterized by the progressive accumulation of extracellular matrix (ECM). The balance between ECM production and degradation is mediated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). TIMP-1 is an important regulator in the synthesis and degradation of ECM. IL-32, a multi-function cytokine, could induce IL-1β, IL-6, IL-8 and other cytokine expressions by activating AP-1, NF-κβ, p38MAPK signal pathways. IL-32 expression is increased in liver tissues of hepatic fibrosis. However, the role of IL-32 in the pathogenesis of liver fibrosis is not thoroughly clear. Recently, it is demonstrated that TIMP-1 expression is induced by the activation of AP-1 signal pathway. So we assayed the effect of IL-32 on TIMP-1 expression by LX-2 cells (one of HSCs cell lines) in the present study. We found that IL-32 could induce TIMP-1 expression by LX-2 cells at a dose-dependent manner. IL-32 could increase TIMP-1 promoter activity and induce TIMP-1 expression by activating AP-1 signal pathway. Moreover, the increase of TIMP-1 expression could promote the migration of LX-2 cells. In conclusion, we believe that IL-32 might be involved in the pathogenesis of hepatic fibrosis by inducing TIMP-1 expression.