| First Author | You JS | Year | 2021 |
| Journal | Cell Rep | Volume | 34 |
| Issue | 1 | Pages | 108594 |
| PubMed ID | 33406419 | Mgi Jnum | J:304135 |
| Mgi Id | MGI:6694811 | Doi | 10.1016/j.celrep.2020.108594 |
| Citation | You JS, et al. (2021) ARHGEF3 Regulates Skeletal Muscle Regeneration and Strength through Autophagy. Cell Rep 34(1):108594 |
| abstractText | Skeletal muscle regeneration after injury is essential for maintaining muscle function throughout aging. ARHGEF3, a RhoA/B-specific GEF, negatively regulates myoblast differentiation through Akt signaling independently of its GEF activity in vitro. Here, we report ARHGEF3's role in skeletal muscle regeneration revealed by ARHGEF3-KO mice. These mice exhibit indiscernible phenotype under basal conditions. Upon acute injury, however, ARHGEF3 deficiency enhances the mass/fiber size and function of regenerating muscles in both young and regeneration-defective middle-aged mice. Surprisingly, these effects occur independently of Akt but via the GEF activity of ARHGEF3. Consistently, overexpression of ARHGEF3 inhibits muscle regeneration in a Rho-associated kinase-dependent manner. We further show that ARHGEF3 KO promotes muscle regeneration through activation of autophagy, a process that is also critical for maintaining muscle strength. Accordingly, ARHGEF3 depletion in old mice prevents muscle weakness by restoring autophagy. Taken together, our findings identify a link between ARHGEF3 and autophagy-related muscle pathophysiology. |
