AUTHOR=Yang Meng-Ge , Zhang Qing , Wang Hong , Ma Xue , Ji Suqiong , Li Yue , Xu Li , Bi Zhuajin , Bu Bitao 

TITLE=The accumulation of muscle RING finger-1 in regenerating myofibers: Implications for muscle repair in immune-mediated necrotizing myopathy

JOURNAL=Frontiers in Neurology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.1032738

DOI=10.3389/fneur.2022.1032738

ISSN=1664-2295

ABSTRACT=<sec><title>Background</title><p>Muscle RING finger-1 (MuRF-1) plays a key role in the degradation of skeletal muscle proteins. We hypothesize the involvement of MuRF-1 in immune-mediated necrotizing myopathy (IMNM).</p></sec><sec><title>Methods</title><p>Muscle biopsies from patients with IMNM (<italic>n</italic> = 37) were analyzed and compared to biopsies from patients with dermatomyositis (DM, <italic>n</italic> = 13), dysferlinopathy (<italic>n</italic> = 9) and controls (<italic>n</italic> = 7) using immunostaining.</p></sec><sec><title>Results</title><p>MuRF-1 staining could be observed in IMNM, DM and dysferlinopathy biopsies, whereas the percentage of MuRF-1 positive myofibers was significantly higher in IMNM than in dysferlinopathy (<italic>p</italic> = 0.0448), and positively correlated with muscle weakness and disease activity in IMNM and DM. Surprisingly, MuRF-1 staining predominantly presented in regenerating fibers but not in atrophic fibers. Moreover, MuRF-1-positive fibers tended to be distributed around necrotic myofibers and myofibers with sarcolemma membrane attack complex deposition. Abundant MuRF-1 expression in IMNM and DM was associated with rapid activation of myogenesis after muscle injury, whereas relatively low expression of MuRF-1 in dysferlinopathy may be attributed to damaged muscle regeneration.</p></sec><sec><title>Conclusions</title><p>MuRF-1 accumulated in regenerating myofibers, which may contribute to muscle injury repair in IMNM and DM. MuRF-1 staining may help clinicians differentiate IMNM and dysferlinopathy.</p></sec>