Fibrosis mechanisms and updates in potential therapeutic targets in systemic sclerosis.

Semin Arthritis Rheum

Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address:

Published: August 2025


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Article Abstract

Systemic sclerosis (SSc) is a rare, multisystem autoimmune connective tissue disease characterized by microvascular dysfunction, inflammation, and progressive fibrosis. The pathogenesis of SSc is regulated by both epigenetic and genetic factors. Although the pathogenesis is being explored, treatment options, especially for fibrosis, remain limited. Recent clinical trials have made significant progress in targeting key pathways in fibrosis. This review discusses emerging therapeutic strategies, focusing on targets such as TGF-β signaling, oncostatin M/OSM receptor β axis, lysophosphatidic acid, nuclear receptor superfamily, endocannabinoid system, soluble guanylate cyclase, and mesenchymal stem cells, and highlights the potential of these targets to improve patient outcomes in combination with relevant clinical trials.

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http://dx.doi.org/10.1016/j.semarthrit.2025.152811DOI Listing

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