| First Author | Roy A | Year | 2021 |
| Journal | Elife | Volume | 10 |
| PubMed ID | 34812145 | Mgi Jnum | J:328130 |
| Mgi Id | MGI:6833816 | Doi | 10.7554/eLife.73215 |
| Citation | Roy A, et al. (2021) The IRE1/XBP1 signaling axis promotes skeletal muscle regeneration through a cell non-autonomous mechanism. Elife 10:e73215 |
| abstractText | Skeletal muscle regeneration is regulated by coordinated activation of multiple signaling pathways. The unfolded protein response (UPR) is a major mechanism that detects and alleviates protein-folding stresses in the endoplasmic reticulum. However, the role of individual arms of the UPR in skeletal muscle regeneration remain less understood. In the present study, we demonstrate that IRE1alpha (also known as ERN1) and its downstream target, XBP1, are activated in skeletal muscle of mice upon injury. Myofiber-specific ablation of IRE1alpha or XBP1 in mice diminishes skeletal muscle regeneration that is accompanied with reduced number of satellite cells. Ex vivo cultures of myofiber explants demonstrate that ablation of IRE1alpha reduces the proliferative capacity of myofiber-associated satellite cells. Myofiber-specific ablation of IRE1alpha dampens Notch signaling and canonical NF-kappaB pathway in skeletal muscle of adult mice. Finally, targeted ablation of IRE1alpha also reduces Notch signaling, abundance of satellite cells, and skeletal muscle regeneration in the mdx mice, a model of Duchenne muscular dystrophy. Collectively, our experiments suggest that the IRE1alpha-mediated signaling promotes muscle regeneration through augmenting the proliferation of satellite cells in a cell non-autonomous manner. |
