Dexamethasone accelerates muscle regeneration by modulating kinesin-1-mediated focal adhesion signals

Jong Wei Lin, Yi Man Huang, Yin Quan Chen, Ting Yun Chuang, Tien Yun Lan, Yen Wenn Liu, Hung Wei Pan, Li Ru You, Yang Kao Wang, Keng hui Lin, Arthur Chiou, Jean Cheng Kuo

研究成果: Article同行評審

摘要

During differentiation, skeletal muscle develops mature multinucleated muscle fibers, which could contract to exert force on a substrate. Muscle dysfunction occurs progressively in patients with muscular dystrophy, leading to a loss of the ability to walk and eventually to death. The synthetic glucocorticoid dexamethasone (Dex) has been used therapeutically to treat muscular dystrophy by an inhibition of inflammation, followed by slowing muscle degeneration and stabilizing muscle strength. Here, in mice with muscle injury, we found that Dex significantly promotes muscle regeneration via promoting kinesin-1 motor activity. Nevertheless, how Dex promotes myogenesis through kinesin-1 motors remains unclear. We found that Dex directly increases kinesin-1 motor activity, which is required for the expression of a myogenic marker (muscle myosin heavy chain 1/2), and also for the process of myoblast fusion and the formation of polarized myotubes. Upon differentiation, kinesin-1 mediates the recruitment of integrin β1 onto microtubules allowing delivery of the protein into focal adhesions. Integrin β1-mediated focal adhesion signaling then guides myoblast fusion towards a polarized morphology. By imposing geometric constrains via micropatterns, we have proved that cell adhesion is able to rescue the defects caused by kinesin-1 inhibition during the process of myogenesis. These discoveries reveal a mechanism by which Dex is able to promote myogenesis, and lead us towards approaches that are more efficient in improving skeletal muscle regeneration.

原文English
文章編號35
期刊Cell Death Discovery
7
發行號1
DOIs
出版狀態Published - 2021 六月

All Science Journal Classification (ASJC) codes

  • 免疫學
  • 細胞與分子神經科學
  • 細胞生物學
  • 癌症研究

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