Abstract
The appearance of myofibroblasts is hallmark of fibrosis and tissue repair. Myofibroblasts are stromal cells that transition from fibroblastic progenitors by acquiring new contractile function. Platelet-derived growth factor (PDGF) promotes fibrosis and supports tissue repair, but the relationship between PDGF and the myofibroblast phenotype is unclear. Using mice with PDGF receptor α (PDGFRα) gene activation or deletion and mutation-linked lineage tracing, we examine fibroblastic progenitor cell fate during spontaneous fibrosis and wound-induced fibrosis. Unexpectedly, elevated PDGFRα signaling generates fibrosis while inhibiting myofibroblast formation. Non-canonical TGFβ-p38 signaling is blocked by PDGFRα activity, thereby inhibiting myofibroblasts. However, deletion of PDGFRα also inhibits myofibroblasts by reducing SRF activity, which leads to defective wound repair. Our findings suggest a scenario where PDGFRα initially expands the progenitor population for tissue repair and later suppression of PDGFRα in activated progenitors permits their transition to myofibroblast.
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