Abstract
BACKGROUND: Corisin, a microbiota-derived proapoptotic peptide, has emerged as a key mediator of epithelial injury, inflammation, and acute exacerbation in fibrotic lung disease. Although acute corisin inhibition prevents exacerbations in experimental models, its therapeutic impact on established pulmonary fibrosis remains unclear. This study evaluated the short-term efficacy of corisin neutralization in advanced transforming growth factor-β1 (TGF-β1)-driven lung fibrosis. METHODS: Male TGF-β1 transgenic mice with established fibrosis were allocated to computed tomography-matched groups and treated intraperitoneally with an anti-corisin monoclonal antibody (clone 21A) or control IgG every two days for one week. Bronchoalveolar lavage fluid (BALF) analysis, histopathology, assessment of apoptosis, Ashcroft scoring, and lung hydroxyproline quantification were performed on day 8. RESULTS: Anti-corisin treatment significantly reduced BALF inflammatory cell counts, including macrophages and lymphocytes. Histological analyses demonstrated decreased alveolar epithelial apoptosis, reduced collagen deposition, and significantly lower Ashcroft fibrosis scores. Lung hydroxyproline content was also markedly decreased, indicating attenuation of extracellular matrix accumulation. CONCLUSIONS: Short-term neutralization of microbiota-derived corisin rapidly alleviates inflammation, epithelial injury, and fibrotic remodeling in advanced TGF-β1-induced pulmonary fibrosis. These findings identify corisin as an upstream driver of ongoing fibrogenesis and support its potential as a therapeutic target in progressive fibrotic lung disease.