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Antifibrotic Therapeutic Strategies in Systemic Sclerosis: Critical Role of the Wnt/Β-Catenin and Tgf-Β Signal Transduction Pathways As Potential Targets Publisher Pubmed



Bagheri L1 ; Javanbakht M2 ; Malekian S1 ; Ghahderijani BH3 ; Taghipour S4 ; Tanha FD5 ; Ranjkesh M6 ; Cegolon L7, 8 ; Zhao S9
Authors

Source: European Journal of Pharmacology Published:2025


Abstract

Systemic sclerosis (SSc) is a prototypic fibrosing disorder characterized by widespread fibrosis and immune dysregulation. Current evidence highlights the intricate cross-talk between the canonical Wnt/β-catenin signaling pathway and transforming growth factor-beta (TGF-β) signaling, both of which play fundamental roles in the pathogenesis of fibrosis. This review aims to elucidate the central role of the Wnt/β-catenin-TGF-β pathway and TGF-β signal transduction pathway in fibrotic diseases, focusing on SSc. We summarized evidence from cellular biology studies, animal model investigations and clinical observations to provide a comprehensive view of the mechanisms causing pathological fibrosis. In addition, we explore the possibilities of antifibrotic therapeutic strategies against Wnt/β-catenin-TGF-β signaling to counteract fibrosis, delineating approaches for treatment of SSc patients by targeting these interconnected signaling pathways. © 2025 Elsevier B.V.
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