TAZ stimulates liver regeneration through interleukin-6-induced hepatocyte proliferation and inhibition of cell death after liver injury
TAZ stimulates liver regeneration through interleukin-6-induced hepatocyte proliferation and inhibition of cell death after liver injury
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DOI：
10.1096/fj.201801256rr
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发表时间：
2019-05-01
期刊：
影响因子：
4.8
通讯作者：
Hong, Jeong-Ho
中科院分区：
文献类型：
--
作者：
Kim, A. Rum;Park, Jung Il;Hong, Jeong-Ho
作为对肝脏损伤的反应，肝脏经历了一个再生过程，以保持其质量和功能。然而，其再生机制尚未完全阐明。本研究探讨了带有PDZ结合基序的转录共激活因子(TAZ)在肝脏再生中的作用。我们观察到TAZ能刺激肝损伤后的肝再生。在肝部分切除(PHX)或四氯化碳损伤后，肝再生需要TAZ来促进肝细胞增殖和抵抗肝细胞凋亡，而在肝脏特异的TAZ基因敲除(LKO)小鼠中，TAZ的作用减弱。TAZ刺激巨噬细胞浸润，产生IL-6，从而诱导肝再生。在LKO小鼠中，IL-6诱导的信号转导和转录激活子3、ERK和PKB的激活减少。我们还观察到，在PHX后肝再生过程中，LKO小鼠的导管周围纤维化显著增加，这是由于肝细胞凋亡增加所致。我们的结果表明，TAZ通过IL-6诱导的肝细胞增殖和抑制肝损伤后的细胞死亡来刺激肝再生。Kim，A.R.，Park，J.I.，oh，H.T.，Kim，K.M.，Hwang，J.-H.，Jeong，M.G.，Kim，E.-H.，Hwang，E.S.，Hong，J.-H.TAZ通过IL-6诱导的肝细胞增殖和抑制肝损伤后的细胞死亡来刺激肝再生。
In response to liver injury, the liver undergoes a regeneration process to retain its mass and function. However, the regeneration mechanism has not been fully clarified. This study investigated the role of transcriptional coactivator with PDZ-binding motif (TAZ), a Hippo-signaling effector, in liver regeneration. We observed that TAZ stimulates liver regeneration after liver injury. After partial hepatectomy (PHx) or carbon tetrachloride damage, TAZ was required for liver regeneration to increase hepatic cell proliferation and resist hepatic apoptosis, which were decreased in liver-specific TAZ knockout (LKO) mice. TAZ stimulated macrophage infiltration, resulting in IL-6 production, which induced liver regeneration. In LKO mice, IL-6-induced activation of signal transducer and activator of transcription 3, ERK, and PKB was decreased. We also observed that periductal fibrogenesis was significantly increased in LKO mice during liver regeneration after PHx, which was caused by increased hepatic apoptosis. Our results suggest that TAZ stimulates liver regeneration through IL-6-induced hepatocyte proliferation and inhibition of cell death after liver injury.Kim, A. R., Park, J. I., Oh, H. T., Kim, K. M., Hwang, J.-H., Jeong, M. G., Kim, E.-H., Hwang, E. S., Hong, J.-H. TAZ stimulates liver regeneration through interleukin-6-induced hepatocyte proliferation and inhibition of cell death after liver injury.