An FGF2-Derived Short Peptide Attenuates Bleomycin-Induced Pulmonary Fibrosis by Inhibiting Collagen Deposition and Epithelial-Mesenchymal Transition via the FGFR/MAPK Signaling Pathway.

Following the COVID-19 pandemic, the prevalence of pulmonary fibrosis has increased significantly, placing patients at higher risk and presenting new therapeutic challenges. Current anti-fibrotic drugs, such as Nintedanib, can slow the decline in lung function, but their severe side effects highlight the urgent need for safer and more targeted alternatives. This study explores the anti-fibrotic potential and underlying mechanisms of an endogenous peptide (P5) derived from fibroblast growth factor 2 (FGF2), developed by our research team. Using a bleomycin-induced pulmonary fibrosis mouse model, we observed that P5 alleviated fibrosis by inhibiting collagen deposition, as confirmed by CT scans and histological staining. In TGF-β-induced cell models, P5 effectively suppressed collagen deposition and epithelial-mesenchymal transition (EMT). Transcriptome analysis highlighted pathways related to receptor binding, extracellular matrix organization, and cell adhesion, with KEGG analysis confirming FGFR/MAPK signaling inhibition as the primary mechanism underlying its anti-fibrotic effects. In summary, our study demonstrates that P5 significantly attenuates pulmonary fibrosis through the inhibition of EMT, collagen deposition, and FGFR/MAPK signaling, providing a promising therapeutic approach for fibrosis.