Signal transducer and activator of transcription 4 in liver diseases.
Signal transducer and activator of transcription 4 in liver diseases.
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肝脏疾病中的信号转导器和转录激活剂 4
DOI：
10.7150/ijbs.11164
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发表时间：
2015
影响因子：
9.2
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Wang Y;Qu A;Wang H
STAT4是定位于细胞质的信号转导子和转录激活子（STAT）分子家族的成员。STAT4经磷酸化、二聚化、转位至细胞核后，作为转录因子调节多种基因的表达。STAT4激活几乎在几种肝损伤小鼠模型的肝脏以及慢性肝病的人类肝脏中检测到。STAT4基因多态性与慢性丙型肝炎、药物性肝损伤（DILI）、原发性胆汁性肝硬化（PBC）、HCV相关性肝纤维化和肝细胞癌（HCC）的抗病毒反应有关。然而，STAT4在肝脏疾病发病机制中的作用仍不完全清楚。本文就STAT4及其相关细胞因子在肝脏疾病中的作用，特别是在调节肝脏抗病毒反应、炎症、增殖、凋亡和肿瘤发生等方面的研究进展作一综述。靶向STAT4信号通路可能是开发治疗肝炎的治疗方法以防止肝硬化和肝癌等进一步损伤的有前途的策略。
STAT4 is a member of the signal transducer and activator of transcription (STAT) family of molecules that localizes to the cytoplasm. STAT4 regulates various genes expression as a transcription factor after it is phosphorylated, dimerizes and translocates to the nucleus. STAT4 activation is detected virtually in the liver of several mouse models of liver injury, as well as the human liver of chronic liver diseases. STAT4 gene polymorphism has been shown to be associated with the antiviral response in chronic hepatitis C and drug-induced liver injury (DILI), primary biliary cirrhosis (PBC), HCV-associated liver fibrosis and in hepatocellular carcinoma (HCC). However, the roles of STAT4 in the pathogeneses of liver diseases are still not understood entirely. This review summarizes the recent advances on the functional roles of STAT4 and its related cytokines in liver diseases, especially in regulating hepatic anti-viral responses, inflammation, proliferation, apoptosis and tumorigenesis. Targeting STAT4 signaling pathway might be a promising strategy in developing therapeutic approaches for treating hepatitis in order to prevent further injury like cirrhosis and liver cancer.
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