1. Department of Infectious Diseases, Peking University First Hospital, Beijing 100034;
3. Institute of Hypoxic Disease, School of Basic Medical Sciences, Capital Medical University, Beijing 100069 ; 4. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Int J Biol Sci. 2015 Feb 27;11(4):448-55. doi: 10.7150/ijbs.11164. eCollection 2015.
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.
STAT4 是信号转导和转录激活因子（STAT）家族的成员，位于细胞质中。STAT4 在磷酸化、二聚化并转移到细胞核后作为转录因子调节各种基因的表达。几乎在几种肝损伤的小鼠模型的肝脏中，以及慢性肝病患者的人类肝脏中，都可以检测到 STAT4 的激活。STAT4 基因多态性与慢性丙型肝炎和药物性肝损伤（DILI）、原发性胆汁性肝硬化（PBC）、丙型肝炎相关肝纤维化和肝细胞癌（HCC）中的抗病毒反应有关。然而，STAT4 在肝病发病机制中的作用仍不完全清楚。本综述总结了 STAT4 及其相关细胞因子在肝脏疾病中的功能作用的最新进展，特别是在调节肝脏抗病毒反应、炎症、增殖、凋亡和肿瘤发生方面的作用。靶向 STAT4 信号通路可能是开发治疗肝炎的治疗方法的有前途的策略，以防止肝硬化和肝癌等进一步损伤。
