498 Artesunate inhibits RDEB fibrosis by downregulating AKT signaling pathway

Patients with recessive dystrophic epidermolysis bullosa (RDEB) develop multiple skin wounds that heal extensive scarring, contractures, and mitten deformities. RDEB patients display increased pro-fibrotic TGF-β signaling, a distinct gene expression profile, elevated inflammation genes. No specific pharmacological treatment is currently available for fibrosis. Artemisinin its derivatives are anti-malarial medications also exhibit both anti-fibrotic anti-inflammatory activity in animal cell models. In this study, we evaluated the ability of artesunate (ART), derivative artemisinin, to inhibit RDEB-related fibrosis using fibroblasts isolated from patients. treated ART demonstrated reduced markers [collagen I (C1), fibronectin (FIN), connective tissue growth factor (CTGF), alpha smooth muscle actin (α-SMA), periostin, tenascin C] by immunoblot analysis. RT-PCR analysis ART-treated showed mRNA levels genes [tenascin-C, CTGF, TGF-β2, α-SMA], as well IL-6, an known stimulate addition, pro-fibrogenic media assessed ELISA. When compared normal vitro collagen lattice assay, untreated exhibited enhanced contraction activity. ART, however, reversed fibroblast hyper-contractability. Lastly, relevant fibrotic via upregulation PI3K/AKT intracellular signaling pathway. decreased p-AKT abolished activation. These data demonstrate may be non-invasive, readily available, safe, novel therapy reducing scarring improving quality life