Comparative Evaluation of Bleomycin- and Collagen-V-Induced Models of Systemic Sclerosis: Insights into Fibrosis and Autoimmunity for Translational Research.

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by fibrosis, immune dysregulation, and vascular dysfunction, yet its pathogenesis remains incompletely understood. This study compares two widely used animal models of SSc-the bleomycin-induced fibrosis model and the collagen-V-induced autoimmune model-to evaluate their ability to replicate key disease features. In the bleomycin model, consistent cardiac fibrosis was observed across treatment groups despite variability in fibrosis in the skin and lungs, suggesting organ-specific differences in susceptibility. The collagen-V model demonstrated robust autoantibody production against collagen-V, confirming its utility in studying immune activation, though fibrosis was largely confined to the heart. While the bleomycin model excels at mimicking rapid fibrosis and is suitable for testing antifibrotic therapies, the collagen-V model provides insights into antigen-specific autoimmunity. Both models highlight the dynamic nature of fibrosis, where ECM deposition and degradation occur concurrently, complicating its use as a quantitative disease marker. Cardiac fibrosis emerged as a consistent feature in both models, emphasizing its relevance in SSc pathophysiology. Combining these models or refining their design through hybrid approaches, extended timelines, or sex and age adjustments could enhance their translational utility. These findings advance understanding of SSc mechanisms and inform therapeutic development for this challenging disease.