Metformin ameliorates scleroderma via inhibiting Th17 cells and reducing mTOR-STAT3 signaling in skin fibroblasts

Abstract Scleroderma is an autoimmune disease that causes dermal fibrosis. It occurs when collagen accumulates in tissue as a result of persistent inflammation. Th17 cells and pro-inflammatory cytokines such IL-1?, IL-6, IL-17, TNF-? play important roles the pathogenesis scleroderma. Because metformin, medication used to treat diabetes, has effective immunoregulatory functions, we investigated its therapeutic function Mice model bleomycin-induced scleroderma were treated with metformin for 2 weeks. Histological assessment demonstrated protective effects against Metformin decreased expression factors lymphocytes. also mRNA (IL-1?, TNF-?) fibrosis-inducing molecules both vivo vitro. These results suggest treatment anti-inflammatory on lymphocytes via inhibition IL-17 related differentiation, TNF-?. To investigate how modulates inflammatory process skin fibroblasts, measured mTOR-STAT3 signaling fibroblasts found phosphorylated mTOR STAT3 protein by treatment. potential inhibiting activity mediated signaling.