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

IF 5.3 2区医学 Q2 CELL BIOLOGY

Skeletal Muscle Pub Date : 2021-03-15 DOI:10.1186/s13395-021-00262-9

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.

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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

Skeletal Muscle CELL BIOLOGY-

CiteScore

9.10

自引率

0.00%

发文量

审稿时长

12 weeks

期刊介绍： The only open access journal in its field, Skeletal Muscle publishes novel, cutting-edge research and technological advancements that investigate the molecular mechanisms underlying the biology of skeletal muscle. Reflecting the breadth of research in this area, the journal welcomes manuscripts about the development, metabolism, the regulation of mass and function, aging, degeneration, dystrophy and regeneration of skeletal muscle, with an emphasis on understanding adult skeletal muscle, its maintenance, and its interactions with non-muscle cell types and regulatory modulators. Main areas of interest include: -differentiation of skeletal muscle- atrophy and hypertrophy of skeletal muscle- aging of skeletal muscle- regeneration and degeneration of skeletal muscle- biology of satellite and satellite-like cells- dystrophic degeneration of skeletal muscle- energy and glucose homeostasis in skeletal muscle- non-dystrophic genetic diseases of skeletal muscle, such as Spinal Muscular Atrophy and myopathies- maintenance of neuromuscular junctions- roles of ryanodine receptors and calcium signaling in skeletal muscle- roles of nuclear receptors in skeletal muscle- roles of GPCRs and GPCR signaling in skeletal muscle- other relevant aspects of skeletal muscle biology. In addition, articles on translational clinical studies that address molecular and cellular mechanisms of skeletal muscle will be published. Case reports are also encouraged for submission. Skeletal Muscle reflects the breadth of research on skeletal muscle and bridges gaps between diverse areas of science for example cardiac cell biology and neurobiology, which share common features with respect to cell differentiation, excitatory membranes, cell-cell communication, and maintenance. Suitable articles are model and mechanism-driven, and apply statistical principles where appropriate; purely descriptive studies are of lesser interest.