Recombinant human neuregulin-1 alleviates immobilization-induced neuromuscular dysfunction via neuregulin-1/ErbB signaling pathway in rat

作者全名："Yang, Jun; Cao, Jun; Min, Su; Li, Ping; Lv, Feng; Ren, Li"

作者地址："[Yang, Jun; Cao, Jun; Min, Su; Li, Ping; Lv, Feng; Ren, Li] Chongqing Med Univ, Affiliated Hosp 1, Dept Anesthesiol, Chongqing 400016, Peoples R China"

通信作者："Min, S (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Anesthesiol, Chongqing 400016, Peoples R China."

来源：ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001015737500001

JCR分区：Q1

影响因子：3.8

年份：2023

卷号：743

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Immobilization; Neuromuscular dysfunction; Nicotinic acetylcholine receptor; Recombinant human neuregulin-1; Myopathy

摘要："Immobilization-induced Neuromuscular Dysfunction (NMD) increases morbidity and mortality of patients in Intensive Care Units. However, the underlying mechanism of NMD remain poorly elucidated which limited the development of therapeutic method for NMD. Here we developed an immobilization rat model and tested the hypothesis that decreased expression of NRG-1, abnormal expression and distribution of nicotinic acetylcholine receptors (nAChRs) in skeletal muscle caused by immobilization can lead to NMD. To investigate the role of NRG-1/ErbB pathway on immobilization-induced NMD, exogenous recombinant human neuregulin-1 (rhNRG-1) was used to increase the expression of NRG-1 in skeletal muscle during immobilization. It was observed rhNRG-1 significantly alleviated the muscle loss and enhanced the expression of e-nAChR, while diminished the expres-sion of & gamma;-and & alpha;7-nAChR and NMD. Interestingly, ErbB inhibitor PD158780 blocked the protective effects of rhNRG-1. Collectively, the results of present study suggested that rhNRG-1 attenuated immobilization-induced muscle loss and NMD, suppressed & gamma;-and & alpha;7-nAChR production, enhanced e-nAChR synthesis via activating NRG-1/ErbB pathway. Taken together, our findings provide novel insights into NMD contribution, suggesting that the rhNRG-1 is a promising therapy to protect against immobilization-induced myopathy."

基金机构："Chongqing Natural Science Foundation project [CSTB2022NSCQ-MSX0075]; Program for Youth Innovation in Future Medicine, Chongqing Medical University [W0168]; Central Subsidy fund for Health Personnel Training (Anesthesiology Department; Key Professional Base for Standardized Training of Resident Doctors [1-02-02-czzx2116]; National Nature Science Foundation of China [81471282]; WU JIEPING Medical Foundation [320.6750.16071]; TIANPU research program [UF201302]"

基金资助正文："This work was supported by Chongqing Natural Science Foundation project (CSTB2022NSCQ-MSX0075) , Program for Youth Innovation in Future Medicine, Chongqing Medical University (W0168) , Central Subsidy fund for Health Personnel Training (Anesthesiology Department, Key Professional Base for Standardized Training of Resident Doctors. No.1-02-02-czzx2116) , National Nature Science Foundation of China (No. 81471282) , WU JIEPING Medical Foundation (No. 320.6750.16071) and the TIANPU research program (UF201302) ."