Abstract
BackgroundSarcopenia 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.MethodsBy 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).ResultsThe 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.ConclusionsWe 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.
Highlights
Sarcopenia is a common skeletal disease related to myogenic disorders and muscle atrophy
We demonstrated that miR-1290 enhanced C2C12 myogenic differentiation and inhibited myotube atrophy in vitro by targeting Forkhead Box O3 (FOXO3) via the Protein kinase B (AKT)/P70 pathway
MiR-1290 expression is negatively correlated with muscle atrophy Through analyzing the serum expression of miR-1290 via real-time polymerase chain reaction (RT-PCR), we concluded that the miR-1290 level of muscle atrophy patients was markedly lower compared with normal controls (Fig. 1a)
Summary
Sarcopenia is a common skeletal disease related to myogenic disorders and muscle atrophy. Metabolism, and endocrine functions [2] and participates in most activities of the human body. Muscle atrophy is a common skeletal disease characterized by muscle wasting or loss of muscle fibers. The causes of muscle atrophy include metabolic diseases or toxins, such as diabetes, AIDS, toxic drugs, and insufficient kidney function [4]. Clinical strategies to treat skeletal muscle atrophy have included surgery, such as free muscle transfer; as well as pharmacology intervention; rehabilitation, such as radiation, muscle stimulation, and manual therapy; and myogenic stem cell transplantation. Despite numerous advances in the past, current clinical strategies have not achieved full muscle function restoration [5]. The above treatments are often accompanied by side effects [6]
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