| First Author | Wang K | Year | 2024 |
| Journal | Stem Cell Reports | Volume | 19 |
| Issue | 4 | Pages | 501-514 |
| PubMed ID | 38552635 | Mgi Jnum | J:348941 |
| Mgi Id | MGI:7640998 | Doi | 10.1016/j.stemcr.2024.02.010 |
| Citation | Wang K, et al. (2024) MST1/2 regulates fibro/adipogenic progenitor fate decisions in skeletal muscle regeneration. Stem Cell Reports 19(4):501-514 |
| abstractText | Defective skeletal muscle regeneration is often accompanied by fibrosis. Fibroblast/adipose progenitors (FAPs) are important in these processes, however, the regulation of FAP fate decisions is unclear. Here, using inducible conditional knockout mice, we show that blocking mammalian Ste20-like kinases 1/2 (MST1/2) of FAPs prevented apoptosis and reduced interleukin-6 secretion in vivo and in vitro, which impaired myoblast proliferation and differentiation, as well as impaired muscle regeneration. Deletion of Mst1/2 increased co-localization of Yes-associated protein (YAP) with Smad2/3 in nuclei and promoted differentiation of FAPs toward myofibroblasts, resulting in excessive collagen deposition and skeletal muscle fibrosis. Meanwhile, inhibition of MST1/2 increased YAP/Transcriptional co-activator with PDZ-binding motif activation, which promoted activation of the WNT/beta-catenin pathway and impaired the differentiation of FAPs toward adipocytes. These results reveal a new mechanism for MST1/2 action in disrupted skeletal muscle regeneration and fibrosis via regulation of FAP apoptosis and differentiation. MST1/2 is a potential therapeutic target for the treatment of some myopathies. |
