文献类型：期刊文献

英文题名：Systemic effect of FHL1 on neuromuscular junction and myotube formation via insulin-like growth factor and myostatin signaling pathways

作者：Wu, Jiamei[1];Zhao, Kai[1];Du, Zengmin[1];Chen, Ying[1];Zhang, Feixu[1];Jiang, Wei[1];Zheng, Jing[1];Wu, Xia[1];Shen, Chengyong[2];Xiao, Xiao[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai, Peoples R China;[2]Zhejiang Univ, Inst Translat Med, Hangzhou, Peoples R China

年份：2021

卷号：537

起止页码：125

外文期刊名：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000609438800018)】；

基金：This study was supported by National Natural Science Foundation of China (31901052), Zhejiang Provincial Natural Science Foundation of China (LR17H090001) and Fundamental Research Funds for the Central Universities.

语种：英文

摘要：Four-and-a-half LIM domain protein 1 (FHL1) is a member of the FHL protein family that serves as a scaffold protein to maintain normal cellular structure and function. Its mutations have been implicated in multiple muscular diseases. These FHL1 related myopathies are characterized by symptoms such as progressive muscle loss, rigid or bent spine, even cardiac or respiratory failure in some patients, which implies pathological problems not only in muscles, but also in the nervous system. Moreover, decreased FHL1 protein level has been found in patients with FHL1 mutations, indicating the protein loss-of-function as a pathological cause of such diseases. These findings suggest the significance of understanding the systemic role of FHL1 in the homeostasis of nervous system and muscle. Here we reported that Fhl1 loss in C2C12 myotubes obscured acetylcholine receptor (AChR) clustering in addition to myotube fusion, which was associated with impaired MuSK phosphorylation. Mechanistically, myostatin-SMAD2/3 signaling was enhanced, whereas IGF-PI3K-AKT signaling was suppressed in Fhl1(-/-) C2C12 myotubes. Reversion of these molecular alterations rescued AChR clustering and differentiation deficits. These data outline a systemic regulation of AChR clustering and myotube fusion by FHL1, which may offer clues for mechanism study and development of therapeutic strategies to treat FHL1 related myopathies. (C) 2020 Elsevier Inc. All rights reserved.