Fibroblasts expressing PIEZO2 mechanoreceptor in keloids possibly cause alloknesis and short-term recurrence after surgical resection [scRNA-seq]

Keloids are scar tissue that can develop under tensile stress and manifest the tactile itch called alloknesis due to the heterogeneous course. But the molecular and cellular mechanisms underlying the pathology of keloid have been still unknown. Here, we found that unique fibroblast subpopulation that have dense-core granules with enhanced expression of PIEZO2 in the dermal layer of keloid tissue with alloknesis, a pressure-tactile itch. PIEZO2-expressed fibroblasts showed enhanced expression of COL1A1, COL1A2 and COL3A1. Gene expression profile analysis of fibrous disease tissues could distinguish the keloid cases by higher PIEZO2, which correlated with collagen COL1A1, COL1A2, and COL3A1 gene expression, not only from the keloid cases with lower PIEZO2 expression but also from the lymphedema cases where massive fibroblast proliferation appears. Notably, patients with the keloid accompanied by higher expression of PIEZO2 showed a significantly shorter time to recurrence after keloidectomy in patients with the keloids (4/5 vs. 0/5, p = 0.047). Thus, a unique subset of PIEZO2-positive fibroblasts may be involved in a keloid pathology and be a potent therapeutic target for the intractable keloids.