Antifibrotic therapeutic strategies in systemic sclerosis: Critical role of the Wnt/β-catenin and TGF-β signal transduction pathways as potential targets

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 by which these pathways cause pathological fibrosis. In addition, we explore the possibilities of antifibrotic therapeutic strategies against Wnt/β-catenin-TGF-β signaling to counteract fibrosis. We aim to delineate approaches towards effectively treating fibrosis in SSc by targeting these interconnected signaling pathways.