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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
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Authors Affiliations
  1. 1. Department of Internal Medicine, Shahid Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  2. 2. Nephrology and Urology Research Center, Clinical Science Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
  3. 3. Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Hormozgan University of Medical Sciences, Bandar Abbas, Iran
  5. 5. Department of Infertility, Yas Hospital, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Student Research Committee, Baqiyatallah University of Medical Sciences, Tehran, Iran
  7. 7. Department of Medical, Surgical & Health Sciences, University of Trieste, Trieste, 34128, Italy
  8. 8. Public Health Unit, University Health Agency Giuliano-Isontina (ASUGI), Trieste, 34148, Italy
  9. 9. School of Public Health, Tianjin Medical University, Tianjin, 300070, China

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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