Peptidomic Analysis Reveals that Novel Peptide LDP2 Protects Against Hepatic Ischemia/Reperfusion Injury  

作　　者：Qun Bao Zhengxin Wang Sheng Cheng Jin Zhang Qiuli Liu Yunpeng Zhang Daqing Cheng Xirong Guo Xingyun Wang Bo Han Peng Sun 

机构地区：[1]Department of General Surgery,Tongren Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China [2]Key Laboratory for Translational Research and Innovative Therapeutics of Gastrointestinal Oncology,Hongqiao International Institute of Medicine,Tongren Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China [3]Department of General Surgery,Huashan Hospital,Fudan University,Shanghai,China [4]Institute of Organ Transplantation,Fudan University,Shanghai,China [5]Department of Anesthesiology and SICU,Xinhua Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China

出　　处：《Journal of Clinical and Translational Hepatology》2023年第2期405-415,共11页临床与转化肝病杂志（英文版）

基　　金：supported by National Natural Science Foundation of China (82070634,82002495);Shanghai Natural Science Foundation (20ZR1451700);SJTU CrossDisciplinary Research Fund in Medicine and Engineering (YG2022QN117);Shanghai Key Medical Specialty Fund (ZK2019A15);Research Fund of Key Laboratory for Translational Research and Innovative Therapeutics of Gastrointestinal Oncology (ZDSYS-2021-04);National Key Research and Development Program (2021YFC2701903).

摘　　要：Background and Aims:Hepatic ischemia/reperfusion(I/R)injury has become an inevitable issue during liver transplantation,with no effective treatments available.However,peptide drugs provide promising regimens for the treatment of this injury and peptidomics has gradually attracted increasing attention.This study was designed to analyze the spectrum of peptides in injured livers and explore the potential beneficial peptides involved in I/R injury.Methods:C57BL/6 mice were used to establish a liver I/R injury animal model.Changes in peptide profiles in I/R-injured livers were analyzed by mass spectrometry,and the functions of the identified peptides were predicted by bioinformatics.AML12 cells were used to simulate hepatic I/R injury in vitro.After treatment with candidate liver-derived peptides(LDPs)1–10,the cells were collected at various reperfusion times for further study.Results:Our preliminary study demonstrated that 6 h of reperfusion caused the most liver I/R injury.Peptidomic results suggested that 10 down-regulated peptides were most likely to alleviate I/R injury by supporting mitochondrial function.Most importantly,a novel peptide,LDP2,was identified that alleviated I/R injury of AML12 cells.It increased cell viability and reduced the expression of inflammation-and apoptosis-related proteins.In addition,LDP2 inhibited the expression of proteins related to autophagy.Conclusions:Investigation of changes in the profiles of peptides in I/R-injured livers led to identification of a novel peptide,LDP2 with potential function in liver protection by inhibiting inflammation,apoptosis,and autophagy.

关 键 词：Hepatic ischemia/reperfusion(I/R)injury PEPTIDOMICS Peptide LDP2 Apoptosis Autophagy 

分 类 号：R575[医药卫生—消化系统]