ArticleJCI insight2025
TNF-α represses fibroblast to myofibroblast transition through the histone methyltransferase Setdb2.
Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
3 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Effects and potential mechanisms of astragaloside IV in animal models of renal fibrosis: a systematic review and meta-analysis.Frontiers in pharmacology · 2026Pooled it
- Dual-Targeting Biomimetic Nanozymes Loaded Microneedle Patch Promotes Scarless Wound Healing Through Anti-Inflammatory and Anti-Fibrotic Effects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Single-cell transcriptomics-guided dynamic hydrogel delivery of artemisia argyi-derived EVs relieves ER stress and promotes diabetic wound regeneration.Journal of nanobiotechnology · 2026Article
Corrections and comments
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Authors and funding
16 authors.
Funding
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 Setdb2 and downregulated myofibroblast genes; inhibition of the TNF-α receptor reduced the upregulation of Setdb2. In diabetes, we showed that TNF-α signaling was increased in wound fibroblasts, which functions to increase Setdb2 expression and represses fibroblast to myofibroblast transition. Fibroblast-specific knockdown of SETDB2 and therapeutic inhibition of JAK1,3/STAT3 improved diabetic wound repair, where wound fibroblasts expressed increased myofibroblast genes. This study is the first to our knowledge to identify an epigenetic mechanism for reduced fibroblast to myofibroblast transition in diabetic wounds. Therapeutic targeting of the TNF-α/STAT3/SETDB2 axis in wound fibroblasts may improve diabetic wound healing.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.