GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE303nnn/GSE303181/primary200OKTranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE303181GEOGSEfalseSTC-1 Attenuates Scar Formation via PI3K/AKT Pathway Activation and Immune ModulationObjective: To investigate the role of Stanniocalcin-1 (STC-1) in scar formation and elucidate its underlying mechanisms in regulating fibroblast activity, immune microenvironment, oxidative stress, and PI3K/AKT signaling. Approach: A combination of clinical sample analysis, in vitro experiments using NIH-3T3 fibroblasts and macrophage co-culture models, RNA sequencing, and in vivo full-thickness wound mouse models were employed. The effects of recombinant human STC-1 and STC-1 overexpression were evaluated on fibroblast function, extracellular matrix remodeling, inflammatory response, and scar formation. The impact on PI3K/AKT signaling was assessed by Western blot analysis. Results: STC-1 was specifically overexpressed in keloid tissues, primarily in fibroblasts, and its expression was upregulated by hypoxia in a HIF-1α–dependent manner. In vitro, STC-1 suppressed fibroblast proliferation, migration, and LPS-induced inflammation, while alleviating oxidative stress and mitochondrial dysfunction. STC-1 also promoted angiogenesis and induced M2 macrophage polarization. In vivo, STC-1 reduced scar size, improved collagen organization, modulated immune cell infiltration by activating the PI3K/AKT signaling pathway. Innovation: This study identifies STC-1 as a novel immunoregulatory and anti-fibrotic factor in scar pathogenesis. It highlights that STC-1 not only affects fibroblast function but also remodels the immune microenvironment through PI3K/AKT activation. Conclusion: STC-1 exerts anti-fibrotic, anti-inflammatory, antioxidant, and immunomodulatory effects during scar formation by activating the PI3K/AKT signaling pathway, highlighting its therapeutic potential in the treatment of pathological scars.2026/08/01GSE303181GSM9119920GSM9119910GSM9119919GSM9119909GSM9119917GSM9119918GSM9119915GSM9119916GSM9119913GSM9119914GSM9119911GSM911991230215303181Mus musculus