| First Author | Yao L | Year | 2022 |
| Journal | Cell Rep | Volume | 40 |
| Issue | 7 | Pages | 111192 |
| PubMed ID | 35977484 | Mgi Jnum | J:330812 |
| Mgi Id | MGI:7332650 | Doi | 10.1016/j.celrep.2022.111192 |
| Citation | Yao L, et al. (2022) Temporal control of PDGFRalpha regulates the fibroblast-to-myofibroblast transition in wound healing. Cell Rep 40(7):111192 |
| abstractText | Fibroblasts differentiate into myofibroblasts by acquiring new contractile function. This is important for tissue repair, but it also contributes to organ fibrosis. Platelet-derived growth factor (PDGF) promotes tissue repair and fibrosis, but the relationship between PDGF and myofibroblasts is unclear. Using mice with lineage tracing linked to PDGF receptor alpha (PDGFRalpha) gene mutations, we examine cell fates during skin wound healing. Elevated PDGFRalpha signaling increases proliferation but unexpectedly delays the fibroblast-to-myofibroblast transition, suggesting that PDGFRalpha must be downregulated for myofibroblast differentiation. In contrast, deletion of PDGFRalpha decreases proliferation and myofibroblast differentiation by reducing serum response factor (SRF) nuclear localization. Consequences of SRF deletion resemble PDGFRalpha deletion, but deletion of two SRF coactivators, MRTFA and MRTFB, specifically eliminates myofibroblasts. Our findings suggest a scenario where PDGFRalpha signaling initially supports proliferation of fibroblast progenitors to expand their number during early wound healing but, later, PDGFRalpha downregulation facilitates fibroblast differentiation into myofibroblasts. |
