GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE333nnn/GSE333609/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE333609GEOGSEfalseScutellarein accelerates diabetic wound healing by inhibiting P2RX1 and rescuing mitochondrial dysfunction and oxidative stress in fibroblastsBackground: Diabetic wounds are a major complication of diabetes mellitus and heal poorly due to persistent inflammation, fibroblast dysfunction, oxidative stress, mitochondrial injury, and impaired angiogenesis. Scutellarein (SCU) is a natural flavonoid with demonstrated anti-inflammatory, antioxidant, and fibroblast-relevant bioactivities, but its effects on diabetic wound repair and the underlying molecular mechanisms remain poorly defined. Methods: A streptozotocin-induced diabetic mouse cutaneous wound model was used to evaluate the effects of topical SCU treatment on wound closure, epithelial repair, and collagen deposition. In vitro, an H₂O₂-induced oxidative injury model in fibroblasts was employed to assess SCU-mediated protection on migration, viability, redox balance, and mitochondrial structure and function. Transcriptomics (RNA-seq) was performed to identify SCU-responsive molecular pathways, and SCU-P2RX1 molecular docking combined with ATP rescue experiments was used to interrogate a P2RX1–calcium axis. Results: SCU accelerated diabetic wound closure and improved epithelial gap, collagen deposition, fibroblast-like cell proliferation, and angiogenesis in vivo. In vitro, SCU promoted fibroblast migration, suppressed H₂O₂-induced cell death, reduced intracellular ROS, restored mitochondrial morphology and membrane potential, and preserved ATP production. RNA-seq revealed that SCU downregulated P2rx1 and enriched calcium-transport, mitochondrial, and wound-healing pathways. Molecular docking predicted SCU binding to P2RX1 with a docking score of ΔG = −9.2 kcal/mol, and ATP addition reversed the SCU-mediated suppression of calcium overload, mitochondrial depolarization, and inflammatory gene expression.2026/06/02GSE333609GSM9769781GSM9769782GSM9769780GSM9769778GSM9769779GSM976977724247333609Mus musculus