Nogo-A regulates myogenesis via interacting with Filamin-C

• Main Authors: SunYoung Park, Ji-Hwan Park, Un-Beom Kang, Seong-Kyoon Choi, Ahmed Elfadl, H. M. Arif Ullah, Myung-Jin Chung, Ji-Yoon Son, Hyun Ho Yun, Jae-Min Park, Jae-hyuk Yim, Seung-Jun Jung, Sang-Hyup Kim, Young-Chul Choi, Dae-Seong Kim, Jin-Hong Shin, Jin-Sung Park, Keun Hur, Sang-Han Lee, Eun-Joo Lee, Daehee Hwang, Kyu-Shik Jeong
• Format: Article
• Language: English
• Published: Nature Publishing Group 2021-01-01
• Series: Cell Death Discovery
• Online Access: https://doi.org/10.1038/s41420-020-00384-x

Abstract Among the three isoforms encoded by Rtn4, Nogo-A has been intensely investigated as a central nervous system inhibitor. Although Nogo-A expression is increased in muscles of patients with amyotrophic lateral sclerosis, its role in muscle homeostasis and regeneration is not well elucidated. In this study, we discovered a significant increase in Nogo-A expression in various muscle-related pathological conditions. Nogo−/− mice displayed dystrophic muscle structure, dysregulated muscle regeneration following injury, and altered gene expression involving lipid storage and muscle cell differentiation. We hypothesized that increased Nogo-A levels might regulate muscle regeneration. Differentiating myoblasts exhibited Nogo-A upregulation and silencing Nogo-A abrogated myoblast differentiation. Nogo-A interacted with filamin-C, suggesting a role for Nogo-A in cytoskeletal arrangement during myogenesis. In conclusion, Nogo-A maintains muscle homeostasis and integrity, and pathologically altered Nogo-A expression mediates muscle regeneration, suggesting Nogo-A as a novel target for the treatment of myopathies in clinical settings.