system
Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Disease Models, Animal, Feedback, Physiological, Gene Expression, Hepatocytes, Humans, Liver, Macrophages, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, NF-kappa B, RNA, Messenger, Receptor-Like Protein Tyrosine Phosphatases, Class 3, Reperfusion Injury, Signal Transduction, src-Family Kinases.
user
Does pTPRO play a dual role in hepatic ischemia reperfusion injury through feedback activation of NF-κB? Context: Nuclear factor-κB (NF-κB) 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-κB pathway. In this study, we aimed to determine the change and function of PTPRO in hepatocytes and macrophages during IR. Clinical patients with benign liver condition undergoing liver surgery were recruited in our study. Wild type (WT) and ptpro(-/-) C57BL/6 mice were processed to construct hepatic IR models. Isolated mouse hepatocytes and macrophages were treated with peroxide or TNFα in vitro. 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-κB up-regulated PTPRO transcription. Using ptpro(-/-) mice and primary cells, we found that PTPRO deficiency resulted in reduction of NF-κB activation in both hepatocytes and macrophages and was correlated to c-Src phosphorylation; PTPRO in hepatocytes alleviated, but PTPROt in macrophages exacerbated IR injury.
assistant
PTPRO activates NF-κB in a positive feedback manner, and plays a dual role in hepatic IR injury. Final Decision: yes