TGF-β1 and VEGF signaling in benign vocal fold lesions: a structured narrative review

Abstract Background Benign vocal fold lesions, particularly vocal fold polyps and nodules, are common causes of dysphonia and are increasingly associated with dysregulated wound healing processes involving fibrosis and angiogenesis. Transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF) have been proposed as important mediators of tissue remodeling in these lesions. Objective To summarize current molecular and translational evidence regarding the potential roles of TGF-β1 and VEGF signaling pathways in benign vocal fold lesions. Methods A structured narrative review of the literature was conducted using PubMed, Scopus, and Web of Science databases through January 2026. Studies investigating molecular signaling mechanisms, tissue expression patterns, experimental models, and therapeutic implications related to TGF-β1 and VEGF in benign vocal fold pathology were reviewed. Results Available evidence suggests that TGF-β1 may contribute to fibroblast activation, extracellular matrix remodeling, and fibrosis, while VEGF appears to participate in angiogenesis, vascular permeability, and stromal edema. The strongest direct evidence currently exists for vocal fold polyps and, to a lesser extent, vocal nodules. Evidence regarding cysts and granulomas remains limited and largely indirect. Experimental and translational studies also suggest interactions between inflammatory signaling, epithelial injury, hypoxia-related pathways, and stromal remodeling. Conclusions Current evidence supports a possible role for TGF-β1 and VEGF signaling in fibrotic and angiogenic remodeling of benign vocal fold lesions, particularly vocal fold polyps. However, further larynx-specific mechanistic and clinical studies are required to clarify their pathogenic significance and potential therapeutic relevance.