Recombinant Human Annexin A5 Ameliorates Localized Scleroderma by Inhibiting the Activation of Fibroblasts and Macrophages

The study demonstrates that recombinant human Annexin A5 (AnxA5) has significant anti-fibrotic and anti-inflammatory effects in treating localized scleroderma (LoS). AnxA5 inhibits the TGF-β/Smad2 signaling pathway in dermal fibroblasts, reducing collagen synthesis and secretion, and modulates macrophage activity to decrease inflammation. In murine models, both systemic and topical applications of AnxA5 effectively reduced fibrosis and inflammation, with preventative treatment showing superior efficacy. These findings suggest AnxA5 as a promising therapeutic candidate for LoS and potentially other fibrotic skin diseases, with ongoing research needed to optimize delivery methods and dosage.