Department of Pain, Huadong Hospital, Shanghai Key Laboratory of Clinical Geriatric Medicine, Fudan University, No. 221, West YanAn Rd, Shanghai, 200040, P.R. China.
Department of Osteoporosis and Bone Disease, Huadong Hospital, Research Section of Geriatric Metabolic Bone Disease, Shanghai Geriatric Institute, Shanghai, China.
Skelet Muscle. 2021 Mar 15;11(1):6. doi: 10.1186/s13395-021-00262-9.
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.
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).
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.
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.
肌少症是一种与肌肉生成障碍和肌肉萎缩相关的常见骨骼疾病。目前的临床治疗方法效果有限。我们试图研究 miR-1290 在成肌细胞分化和肌肉萎缩中的作用。
通过转染 miR-1290 进入 C2C12 细胞，我们研究了 miR-1290 是否通过 AKT/P70 信号通路调节成肌细胞分化和肌管萎缩。通过 MHC 染色评估成肌细胞分化。通过 Western blot 探讨分化相关的 MHC、Myod 和 Myog 蛋白水平，以及萎缩相关的 MuRF1 和 Atrogin-1。建立 LPS 诱导的肌肉萎缩大鼠模型。通过 RT-PCR 分析肌肉萎缩患者和正常对照组（NCs）血清中 miR-1290 的水平。
miR-1290 转染组的 MHC 阳性细胞和 MHC、Myod 和 Myog 蛋白水平均增加，表明 miR-1290 促进 C2C12 成肌细胞分化。miR-1290 转染组的肌管直径高于 TNF-α 诱导模型组。Western blot 分析显示，miR-1290 转染组的 MuRF1 和 Atrogin-1 水平低于模型组，表明 miR-1290 可防止成肌细胞细胞萎缩。荧光素酶检测和 Western blot 分析表明，miR-1290 的调节可能是通过 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 模拟物改善了比目鱼肌的丢失并增加了肌肉纤维的横截面积。临床上，肌肉萎缩患者的血清 miR-1290 水平显著降低。
我们发现 miR-1290 通过体外和体内的 Akt/p70/FoxO3 信号增强成肌细胞分化并抑制肌管萎缩。此外，miR-1290 可能是治疗肌少症的潜在治疗靶点。
