Pim-1 kinase protects the liver from ischemia reperfusion injury by regulating dynamics-related protein 1

Pim-1 激酶通过调节动力学相关蛋白 1 保护肝脏免受缺血再灌注损伤

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作者:Yan-Dong Sun, Qing-Guo Xu, De-Shu Dai, Shu-Xian Wang, Xin-Qiang Li, Shang-Heng Shi, Peng Jiang, Yan Jin, Xin Wang, Yong Zhang, Feng Wang, Peng Liu, Bing-Liang Zhang, Tian-Xiang Li, Chuan-Shen Xu, Bin Wu, Jin-Zhen Cai

Abstract

Hepatic ischemia-reperfusion (IR) injury significantly impacts liver transplantation success, yet current treatments remain inadequate. This study explores the role of Proto-oncogene serine/threonine-protein kinase (Pim-1) in liver IR, an area previously unexplored. Utilizing a mouse liver IR in vivo model and a MIHA cell hypoxia-reoxygenation in vitro model, we observed that Pim-1 expression increases following IR, inversely correlating with serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Increased Pim-1 expression stabilizes mitochondrial membranes by modifying Drp1 phosphorylation, reducing mitochondrial fission and apoptosis, thereby mitigating liver damage. Additionally, we discovered that elevated Pim-1 expression is dependent on the trimethylation of histone H3 lysine 9 during liver IR. These findings underscore the importance and potential clinical application of targeting Pim-1 in treating hepatic IR, presenting a novel therapeutic avenue.

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