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Nuclear fragile X mental retardation-interacting protein 1-mediated ribophagy protects T lymphocytes against apoptosis in sepsis

作     者:Peng-Yue Zhao Ren-Qi Yao Li-Yu Zheng Yao Wu Yu-Xuan Li Ning Dong Jing-Yan Li Xiao-Hui Du Yong-Ming Yao 

作者机构:Translational Medicine Research CenterMedical Innovation Research Division and Fourth Medical Center of the Chinese PLA General HospitalBeijing 100853China Department of General SurgeryFirst Medical Center of the Chinese PLA General HospitalBeijing 100853China Department of Burn SurgeryThe First Affiliated Hospital of Naval Medical UniversityShanghai 200433China Department of EmergencyThe Second Hospital of Hebei Medical UniversityShijiazhuang 050000China 

出 版 物:《Burns & Trauma》 (烧伤与创伤(英文))

年 卷 期:2023年第11卷第1期

页      面:72-90页

核心收录:

学科分类:1002[医学-临床医学] 100210[医学-外科学(含:普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学] 

基  金:supported by grants from the National Natural Sciences Foundation of China(Nos.81730057,82130062,81801935) Key Project of Military Medical Innovation Program of Chinese PLA(Nos.18CXZ025,18CXZ026) Provincial Key Project of Medical Science Research of Hebei(20210013) 

主  题:NUFIP1 Ribophagy Sepsis Apoptosis Immunosuppression Autophagy Mitophagy Lymphocyte Lipopolysaccharide 

摘      要:Background:Ribophagy is a selective autophagic process that specifically degrades dysfunctional or superfluous ribosomes to maintain cellular *** ribophagy can ameliorate the immunosuppression in sepsis similar to endoplasmic reticulum autophagy(ERphagy)and mitophagy remains *** study was conducted to investigate the activity and regulation of ribophagy in sepsis and to further explore the potential mechanism underlying the involvement of ribophagy in T-lymphocyte ***:The activity and regulation of nuclear fragile X mental retardation-interacting protein 1(NUFIP1)-mediated ribophagy in T lymphocytes during sepsis were first investigated by western blotting,laser confocal microscopy and transmission electron ***,we constructed lentivirally transfected cells and gene-defective mouse models to observe the impact of NUFIP1 deletion on T-lymphocyte apoptosis and finally explored the signaling pathway associated with T-cell mediated immune response following septic ***:Both cecal ligation and perforation-induced sepsis and lipopolysaccharide stimulation significantly induced the occurrence of ribophagy,which peaked at 24 *** NUFIP1 was knocked down,T-lymphocyte apoptosis was noticeably ***,the overexpression of NUFIP1 exerted a significant protective impact on T-lymphocyte ***,the apoptosis and immunosuppression of T lymphocytes and 1-week mortality rate in NUFIP1 gene-deficient mice were significantly increased compared with those in wild-type *** addition,the protective effect of NUFIP1-mediated ribophagy on T lymphocytes was identified to be closely related to the endoplasmic reticulum stress apoptosis pathway,and PERK-ATF4-CHOP signaling was obviously involved in downregulating T-lymphocyte apoptosis in the setting of ***:NUFIP1-mediated ribophagy can be significantly activated to alleviate T lymphocyte apoptosis through the PERK-ATF4-CHOP pathway

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