TNF-α represses fibroblast to myofibroblast transition through the histone methyltransferase Setdb2.

ABSTRACT: Fibroblast to myofibroblast transition is a critical event required for effective tissue repair. In pathologic wound repair processes, such as type 2 diabetes (T2D), fibroblast to myofibroblast transition is impaired. The exact factors that control this transition in wounds are unclear. Here, using human tissue and murine transgenic models, we show that the histone methyltransferase SETDB2 is elevated in diabetic wound fibroblasts and TNF-α represses fibroblast to myofibroblast transition via Setdb2. We identified that TNF-α increases Setdb2 in fibroblasts via a JAK1,3/STAT3 signaling pathway, where pharmacologic or genetic manipulation of this pathway altered Setdb2 in fibroblasts. We also found that fibroblasts treated with pro-inflammatory macrophage supernatants displayed increased Set

SUBMITTER: Bauer TM 

PROVIDER: S-EPMC12643505 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature