Muscle RING finger-1 facilitates skeletal muscle regeneration via regulating myoblast proliferation and differentiation

BACKGROUND: Muscle RING finger-1 (MuRF-1) serves as a marker of muscle atrophy. However, we have previously shown that MuRF-1 primarily accumulates in regenerating myofibers in muscles from patients with immune-mediated necrotizing myopathy (IMNM). This study was designed to further investigate the underlying mechanisms of MuRF-1 involved in skeletal muscle regeneration. METHODS: MuRF-1 expression and muscle regeneration in muscle biopsies from patients with IMNM were detected using immunostaining and real-time quantitative polymerase chain reaction (RT-qPCR). Biopsies from dermatomyositis (DM), dysferlinopathy, and healthy controls were selected for comparison. Short interfering RNA (siRNA) technique, RT-qPCR, western blot, flow cytometry analysis, and immunostaining were performed to explore the roles of MuRF-1 in human myoblast proliferation and differentiation. RESULTS: Muscle regeneration was activated in muscles of IMNM, DM, and dysferlinopathy, especially in IMNM and DM, compared with healthy controls. MuRF-1 expression strongly correlated with myofiber regeneration. MuRF-1-positive myofibers co-localized with regenerating fibers and highly expressed the myogenic transcription factor MyoG. Moreover, satellite cells (muscle stem cells) were enriched on the surface of these myofibers. In vitro experiments further demonstrated that MuRF-1 expression was upregulated during myogenic differentiation. MuRF-1 knockdown inhibited myoblast proliferation, differentiation, and fusion. Moreover, the expression of cell cycle protein Cyclin A and the myogenic regulatory factor MyoG was significantly decreased. CONCLUSIONS: MuRF-1 is involved in muscle regeneration by regulating myoblast proliferation and differentiation, which may contribute to muscle injury repair in IMNM. This finding provides new insights into the pathophysiological roles of MuRF-1 in muscular disorders.