在实验性自身免疫性重症肌无力的发展过程中,肌纤维类型通过PI3K/Akt信号通路进行切换。

IF 3.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Xinrong Li, Xiuhua Yao, Wei Zhao, Bo Wei, Ran Zhang, Geng Yan, Mingyu Ma, Zhenhai Wang, Xijun Liu, Yumei Liu, Guangyou Wang, Hulun Li, Qingfei Kong, Jinghua Wang, Lili Mu
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引用次数: 0

摘要

骨骼肌作为人体最大的器官之一,在重症肌无力(MG)中具有良好的研究前景。重症肌无力主要表现为全身骨骼肌无力。骨骼肌由两种类型的肌纤维组成。不同的纤维亚型可以相互转换;然而,潜在的机制尚不清楚。本文首先建立了实验性自身免疫性重症肌无力(EAMG)大鼠模型,发现EAMG组骨骼肌纤维萎缩,纤维亚型比例发生变化,经组织学和分子分析证实,EAMG组骨骼肌纤维在高峰阶段由IIa型转变为I型。第二代测序结果预测PI3K-Akt信号通路可能参与了该开关,PI3K-Akt通路相关基因nr4a1、IL2rb、Col1A1和Ddit4的mRNA表达水平存在显著差异。综上所述,本研究表明,通过PI3K-Akt信号通路,MG中肌纤维亚型的转换可能是未来治疗MG相关骨骼肌萎缩的潜在靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Muscle fiber types switched during the development of experimental autoimmune myasthenia gravis via the PI3K/Akt signaling pathway.

As one of the largest organs of our human body, skeletal muscle has good research prospects in myasthenia gravis (MG), the symptoms of which include systemic skeletal muscle weakness. Skeletal muscle is composed of two types of muscle fibers. Different fiber subtypes can be converted into each other; however, the underlying mechanism is not yet clear. In this paper, we firstly established an experimental autoimmune myasthenia gravis (EAMG) rat model and found that the skeletal muscle fibers of the EAMG group were atrophied, with a change in the proportion of fiber subtypes, which switched from type IIa to type I in the EAMG group at the peak stage, as verified by histological and molecular analyses. Second-generation sequencing results predicted that the PI3K-Akt signaling pathway might be involved in the switch, and the mRNA expression levels of the PI3K-Akt pathway-related genesNr4a1, IL2rb, Col1A1 and Ddit4 were significantly different. In conclusion, this study indicates that the switch of muscle fiber subtypes in MG via the PI3K-Akt signaling pathway may be a potential target for the treatment of MG-related skeletal muscle atrophy in the future.

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来源期刊
Molecular immunology
Molecular immunology 医学-免疫学
CiteScore
6.90
自引率
2.80%
发文量
324
审稿时长
50 days
期刊介绍: Molecular Immunology publishes original articles, reviews and commentaries on all areas of immunology, with a particular focus on description of cellular, biochemical or genetic mechanisms underlying immunological phenomena. Studies on all model organisms, from invertebrates to humans, are suitable. Examples include, but are not restricted to: Infection, autoimmunity, transplantation, immunodeficiencies, inflammation and tumor immunology Mechanisms of induction, regulation and termination of innate and adaptive immunity Intercellular communication, cooperation and regulation Intracellular mechanisms of immunity (endocytosis, protein trafficking, pathogen recognition, antigen presentation, etc) Mechanisms of action of the cells and molecules of the immune system Structural analysis Development of the immune system Comparative immunology and evolution of the immune system "Omics" studies and bioinformatics Vaccines, biotechnology and therapeutic manipulation of the immune system (therapeutic antibodies, cytokines, cellular therapies, etc) Technical developments.
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