CD74+ fibroblasts proliferate upon mechanical stretching to promote angiogenesis in keloids

• DOI: 10.1096/fj.202401302r
• Publication Date: 2024-10-14T07:40:46Z
• Authors: Jingheng Zhang; Shuyao Li; Chunmei Kuang; Yunfan Shen; Haibin Yu; Fang Chen; Ruijun Tang; Song Mao; Lu Lv; Min Qi; Jianglin Zhang; Kai Yuan
• Keywords: Keloid; Hypertrophic scars; Immunostaining

Abstract The healing of human skin wounds is susceptible to perturbation caused by excessive mechanical stretching, resulting in enlarged scars, hypertrophic or even keloids predisposed individuals. Keloids are fibro‐proliferative scar tissues that extend beyond the initial wound boundary, consisting actively progressing periphery and quiescent center. stretch‐associated outgrowth enhanced angiogenesis two features keloids. However, which cell population responsible for transducing stimulation progression remains unclear. Herein, through integrative analysis single‐cell RNA sequencing keloids, we identified CD74 + fibroblasts, a previously unappreciated subset fibroblasts with pro‐angiogenic stretch‐induced proliferative capacities, as key player Immunostaining keloid cryosections depicted predominant distribution periphery, interacting vasculature. In vitro tube formation assays on purified ascertained their function. BrdU revealed these cells proliferate upon PIEZO1‐mediated calcium influx downstream ERK AKT signaling. Collectively, our findings propose model wherein serve pivotal drivers progression, fueled activities. Targeting attributes holds promise therapeutic strategy management