MiR-1290 promotes myoblast differentiation and protects against myotube atrophy via Akt/p70/FoxO3 pathway regulation.

IF 8.3 2区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY
Ji Che, Cuidi Xu, Yuanyuan Wu, Peiyu Jia, Qi Han, Yantao Ma, Xiaolei Wang, Yongjun Zheng
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引用次数: 13

Abstract

Background: Sarcopenia is a common skeletal disease related to myogenic disorders and muscle atrophy. Current clinical management has limited effectiveness. We sought to investigate the role of miR-1290 in myoblast differentiation and muscle atrophy.

Methods: By transfecting miR-1290 into C2C12 cells, we investigated whether miR-1290 regulates myogenesis and myotube atrophy via AKT/P70 signaling pathway. MHC staining was performed to assess myoblast differentiation. Differentiation-related MHC, Myod, and Myog protein levels, and atrophy-related MuRF1 and atrogin-1 were explored by western blot. An LPS-induced muscle atrophy rat model was developed. RT-PCR was conducted to analyze miR-1290 serum levels in muscle atrophy patients and normal controls (NCs).

Results: The miR-1290 transfection increased MHC-positive cells and MHC, Myod, and Myog protein levels in the miR-1290 transfection group, demonstrating that miR-1290 promoted C2C12 myoblast differentiation. Myotube diameter in the miR-1290 transfection group was higher than in the TNF-α-induced model group. Western blot analysis showed decreased MuRF1 and atrogin-1 levels in the miR-1290 transfection group compared with the model group, demonstrating that miR-1290 protected against myoblast cellular atrophy. Luciferase assay and western blot analysis showed that miR-1290 regulation was likely caused by AKT/p70/FOXO3 phosphorylation activation. In the LPS-induced muscle atrophy rat model, miR-1290 mimics ameliorated gastrocnemius muscle loss and increased muscle fiber cross-sectional area. Clinically, miR-1290 serum level was significantly decreased in muscle atrophy patients.

Conclusions: We found that miR-1290 enhances myoblast differentiation and inhibits myotube atrophy through Akt/p70/FoxO3 signaling in vitro and in vivo. In addition, miR-1290 may be a potential therapeutic target for sarcopenia treatment.

Abstract Image

Abstract Image

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MiR-1290通过Akt/p70/FoxO3通路调控促进成肌细胞分化,防止肌管萎缩。
背景:肌少症是一种常见的骨骼疾病,与肌原性疾病和肌肉萎缩有关。目前的临床治疗效果有限。我们试图研究miR-1290在成肌细胞分化和肌肉萎缩中的作用。方法:将miR-1290转染到C2C12细胞中,研究miR-1290是否通过AKT/P70信号通路调控肌生成和肌管萎缩。MHC染色评估成肌细胞分化。western blot检测与分化相关的MHC、Myod和Myog蛋白水平,以及与萎缩相关的MuRF1和atrogin-1。建立lps诱导大鼠肌肉萎缩模型。采用RT-PCR方法分析肌萎缩患者和正常对照(nc)的血清miR-1290水平。结果:miR-1290转染组MHC阳性细胞和MHC、Myod、Myog蛋白水平升高,表明miR-1290促进了C2C12成肌细胞分化。miR-1290转染组的肌管直径高于TNF-α-诱导的模型组。Western blot分析显示,与模型组相比,转染miR-1290组的MuRF1和atrogin-1水平降低,表明miR-1290对成肌细胞萎缩具有保护作用。荧光素酶分析和western blot分析显示,miR-1290的调控可能是由AKT/p70/FOXO3磷酸化激活引起的。在lps诱导的肌肉萎缩大鼠模型中,miR-1290模拟改善腓肠肌损失和增加肌纤维横截面积。临床上,肌萎缩患者血清miR-1290水平明显降低。结论:在体外和体内实验中,我们发现miR-1290通过Akt/p70/FoxO3信号通路增强成肌细胞分化,抑制肌管萎缩。此外,miR-1290可能是肌少症治疗的潜在治疗靶点。
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来源期刊
ACS Applied Materials & Interfaces
ACS Applied Materials & Interfaces 工程技术-材料科学:综合
CiteScore
16.00
自引率
6.30%
发文量
4978
审稿时长
1.8 months
期刊介绍: ACS Applied Materials & Interfaces is a leading interdisciplinary journal that brings together chemists, engineers, physicists, and biologists to explore the development and utilization of newly-discovered materials and interfacial processes for specific applications. Our journal has experienced remarkable growth since its establishment in 2009, both in terms of the number of articles published and the impact of the research showcased. We are proud to foster a truly global community, with the majority of published articles originating from outside the United States, reflecting the rapid growth of applied research worldwide.
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