1478 TEM1/endosialin/CD248 promotes pathologic scarring by augmenting TGF-β activity through its receptor stability in dermal fibroblasts

Keloids represent a common form of exaggerated cutaneous scarring that is difficult to prevent or treat effectively. TGF-β has been implicated in driving abnormal wound healing responses and generating excessive extracellular matrix (ECM) deposition but the pathobiology keloids remains poorly understood. Here, we show mRNA protein levels tumor endothelial marker 1 (TEM1/endosialin/CD248), glycosylated type I transmembrane member C-type lectin-like domain superfamily, are highly upregulated keloid fibroblasts tissues. A re-analysis single-cell RNA-sequencing datasets reveals major profibrotic subpopulation greatly expresses TEM1, with expression increasing during fibroblast activation. TEM1 promotes activation, proliferation, ECM production human dermal by enhancing TGF-β1 signaling through binding stabilizing receptors. Global deletion Tem1 markedly reduces amount synthesis inflammation scar mouse model stretch-induced hypertrophic scarring. Our data synergistic effect on pathway significantly contributes activation biology pathologic Targeting may novel therapeutic approach reducing morbidity potentially other forms