Irisin Ameliorates Muscle Atrophy by Inhibiting the Upregulation of the Ubiquitin‒Proteasome System in Chronic Kidney Disease

IF 3.3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Shiyuan Wang, Yajing Pan, Qi Pang, Aihua Zhang
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Abstract

Muscle atrophy is a common complication of chronic kidney disease (CKD). Irisin, a novel muscle cytokine, protects against muscle atrophy, but its specific role in CKD-associated muscle atrophy requires further elucidation. Because the ubiquitin–proteasome system (UPS) plays an important role in CKD muscle atrophy, our study will explore whether irisin affects UPS and alleviate CKD-associated muscle atrophy. In this study, an adenine-fed mouse model of CKD and urotension II (UII)-induced C2C12 myotubes were used as in vivo and in vitro models of muscle atrophy. The results showed that renal function, mouse weight, and the cross-sectional area (CSA) of skeletal muscles were significantly improved in CKD mice treated with irisin. Moreover, irisin effectively mitigated the decreases in phosphorylated Forkhead box O 3a (p-FOXO3A) levels and increases in the levels of E3 ubiquitin ligases, such as muscle RING finger 1 (MuRF1) and muscle atrophy F-box (MAFbx/atrogin1), in both the muscles of CKD mice and UII-induced C2C12 myotubes. In addition, irisin significantly increased the expression levels of myogenic differentiation factor D (MyoD) in the muscles of CKD mice. Our study is the first to demonstrate that irisin ameliorates skeletal muscle atrophy by inhibiting UPS upregulation and improving satellite cell differentiation in CKD.

Abstract Image

鸢尾素通过抑制慢性肾病患者泛素-蛋白酶体系统的上调改善肌肉萎缩状况
肌肉萎缩是慢性肾脏病(CKD)的常见并发症。鸢尾素是一种新型肌肉细胞因子,能防止肌肉萎缩,但它在 CKD 相关肌肉萎缩中的具体作用还需要进一步阐明。由于泛素-蛋白酶体系统(UPS)在 CKD 肌肉萎缩中发挥着重要作用,我们的研究将探讨鸢尾素是否会影响 UPS 并减轻 CKD 相关肌肉萎缩。本研究采用腺嘌呤喂养的 CKD 小鼠模型和尿张力Ⅱ(UII)诱导的 C2C12 肌管作为肌肉萎缩的体内和体外模型。结果表明,使用鸢尾素治疗的 CKD 小鼠的肾功能、小鼠体重和骨骼肌横截面积(CSA)均有明显改善。此外,鸢尾素还能有效缓解CKD小鼠肌肉和UII诱导的C2C12肌管中磷酸化叉头盒O 3a(p-FOXO3A)水平的下降和E3泛素连接酶(如肌肉RING指1(MuRF1)和肌肉萎缩F-box(MAFbx/atrogin1))水平的升高。此外,鸢尾素还能显著提高 CKD 小鼠肌肉中肌生成分化因子 D(MyoD)的表达水平。我们的研究首次证明了鸢尾素能通过抑制 UPS 上调和改善 CKD 中卫星细胞的分化来改善骨骼肌的萎缩。
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来源期刊
Calcified Tissue International
Calcified Tissue International 医学-内分泌学与代谢
CiteScore
8.00
自引率
2.40%
发文量
112
审稿时长
4-8 weeks
期刊介绍: Calcified Tissue International and Musculoskeletal Research publishes original research and reviews concerning the structure and function of bone, and other musculoskeletal tissues in living organisms and clinical studies of musculoskeletal disease. It includes studies of cell biology, molecular biology, intracellular signalling, and physiology, as well as research into the hormones, cytokines and other mediators that influence the musculoskeletal system. The journal also publishes clinical studies of relevance to bone disease, mineral metabolism, muscle function, and musculoskeletal interactions.
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