PTPRO plays a dual role in hepatic ischemia reperfusion injury through feedback activation of NF-魏B

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• 作者：Jiajie Hou ; Yongxiang Xia ; Runqiu Jiang ; Dianyu Chen ; Juan Xu ; Lei Deng ; Xingxu Huang ; Xuehao Wang ; Beicheng Sun
• 关键词：IR ; ischemia reperfusion ; ROS ; reactive oxygen species ; KCs ; kupffer cells ; TNF伪 ; tumor necrosis factor 伪 ; IL-1尾 ; interleukin-1尾 ; NF-魏B ; Nuclear factor-魏B ; JNK ; Jun N-terminal kinase ; I魏B ; inhibitor of NF-魏B ; IKK ; I魏B kinase ; PTPRO ; Protein tyrosine phosphatase receptor type O ; PTP ; phosphotyrosine phosphatase ; STAT ; signal transducers and activators of transcription ; SHP2 ; Src homology domain-containing phosphatase-2 ; HCC ; hepatocellular carcinoma
• 刊名：Journal of Hepatology
• 出版年：February, 2014
• 年：2014
• 卷：60
• 期：2
• 页码：306-312
• 全文大小：1814 K

文摘

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Background & Aims

Nuclear factor-魏B (NF-魏B) activation in hepatocytes and macrophages appeared as a double-edged-sword in hepatic ischemia reperfusion (IR) injury. Protein tyrosine phosphatase receptor type O (PTPRO) was recently identified as a potential activator of c-Src, which can in turn activate the NF-魏B pathway. In this study, we aimed to determine the change and function of PTPRO in hepatocytes and macrophages during IR.

Methods

Clinical patients with benign liver condition undergoing liver surgery were recruited in our study. Wild type (WT) and ptpro^{鈭?鈭?/sup> C57BL/6 mice were processed to construct hepatic IR models. Isolated mouse hepatocytes and macrophages were treated with peroxide or TNF伪 in vitro.}

Results

In human and mouse IR models, PTPRO level was decreased in the early phase but reversed in the late phase. In vitro studies demonstrated that NF-魏B up-regulated PTPRO transcription. Using ptpro^{鈭?鈭?/sup> mice and primary cells, we found that PTPRO deficiency resulted in reduction of NF-魏B activation in both hepatocytes and macrophages and was correlated to c-Src phosphorylation; PTPRO in hepatocytes alleviated, but PTPROt in macrophages exacerbated IR injury.}

Conclusions

PTPRO activates NF-魏B in a positive feedback manner, and plays a dual role in hepatic IR injury.