FOSL1-mediated super-enhancer facilitates pathological scarring.

作者：Yi-Xin Sun, Zhizhuo Chen, Meng-Di Zhang, Haoran Zhang, Tianhao Li, Yashi Li, Zikai Qiu, Jie Li, Mengyuan Zhang, Yucheng Dong, E. Zhang, Mingheng Xue, Ji Wang, Yi Sun, Fengzhou Du, Nanze Yu, Yang Pu, Y. Rinkevich, Xiao Long · 发表于：Cell Reports · 年份：2026 · DOI：10.1016/j.celrep.2026.117667 · 研究领域：Medicine

Abnormal wound healing leads to pathological scar formation, characterized by excessive fibrosis. Despite their clinical relevance, the underlying molecular factors remain poorly understood. Using single-cell RNA sequencing, we identify FOSL1+ keratinocyte subpopulations that expand in hypertrophic scars and keloids. These cells exhibit epithelial-mesenchymal transition features and promote fibrosis by secreting MMP3, a critical mediator of fibroblast activation. Mechanistically, FOSL1 drives MMP3 transcription by engaging a MED-1 associated super-enhancer, amplifying fibroblast activation and inflammation. Importantly, the FOSL1 inhibitor SR11302 reduces scar formation in in vivo xenogenic keloid models, offering a potential therapeutic strategy. Collectively, this study elucidates abnormal tissue repair mechanisms driven by aberrant cellular interactions, providing a theoretical foundation for developing intervention strategies toward scarless healing.