Mechanisms of liver injury.: I.: TNF-α-induced liver injury:: role of IKK, JNK, and ROS pathways
Mechanisms of liver injury.: I.: TNF-α-induced liver injury:: role of IKK, JNK, and ROS pathways
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DOI：
10.1152/ajpgi.00422.2005
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发表时间：
2006-04-01
影响因子：
4.5
通讯作者：
Brenner, DA
中科院分区：
文献类型：
--
作者：
Schwabe, RF;Brenner, DA
TNF-α激活几种细胞内途径以调节炎症、细胞死亡和增殖。在肝脏中，TNF-α不仅是肝毒性的介质，而且还通过驱动肝细胞增殖和肝再生来促进功能性肝脏质量的恢复。本文综述了TNF-α信号转导机制的最新进展，这些机制表明IKK、ROS和JNK通路如何相互作用来调节肝细胞凋亡和增殖。这些途径的激活与刀豆球蛋白A、TNF-α和缺血再灌注诱导的肝损伤以及肝再生和肝癌发生有因果关系。根据最近的研究结果，JNK和IKK的药理学抑制剂和抗氧化剂可能是治疗肝炎、缺血再灌注损伤和肝细胞癌的有前途的新工具。
TNF-alpha activates several intracellular pathways to relgulate inflammation, cell death, and proliferation. In the liver, TNF-alpha is not only a mediator of hepatotoxicity but also contributes to the restoration of functional liver mass by driving hepatocyte proliferation and liver regeneration. This review summarizes recent advances in TNF-alpha signaling mechanisms that demonstrate how the IKK, ROS, and JNK pathways interact with each other to regulate hepatocyte apoptosis and proliferation. Activation of these pathways is causatively linked to liver injury induced by concanavalin A, TNF-alpha, and ischemia-reperfusion and to liver regeneration and hepatocarcinogenesis. In light of recent findings, pharmacological inhibitors of JNK and IKK and antioxidants may be promising new tools for the treatment of hepatitis, ischemia-reperfusion injury, and hepatocellular carcinoma.