Increased Collagen V Triggers Inflammation and Fibrosis in Early Pulmonary Disease of Systemic Sclerosis: Insights from the IMU-COLV Model

Understanding the early stages of pulmonary disease pathogenesis in systemic sclerosis (SSc) is crucial for developing therapeutic strategies to mitigate pulmonary fibrosis progression. Our aim is to evaluate the early stages of pulmonary fibrosis in the IMU-COLV model. This study used the SSc IMU-COLV model in female C57BL/6 mice immunized with collagen V (COLV) emulsified in Freund's adjuvant. Mice were categorized into groups based on immunization duration (15, 30, and 45 days) to assess lymphocyte populations, Factor VIII, VEGF, caspase-3, α-AML, and collagen expression through immunostaining and image analysis. Total collagen content was quantified using 4-hydroxyproline, while α-AML, TGF-β1, and collagen gene expressions were evaluated via RT-qPCR. At day 15, significant increases in CD3+, CD4+, CD8+, and CD20 + lymphocytes, Factor VIII, VEGF, and α-AML were observed, alongside enhanced COLV and Col5α1/Col5α2 gene expressions. Inflammation decreased at day 30; however, by day 45, a nonspecific interstitial pneumonia pattern emerged, with intrapulmonary artery thickening, increased Caspase-3, α-AML, collagen types I and III, Col1α1 and Col3α1 genes, and total collagen levels. Furthermore, vimentin, α-AML, and TGF-β1 gene expressions were higher in the 45-day group. The IMU-COLV model exhibits an early inflammatory phase at day 15, with COLV deposition, leading to pulmonary remodeling and fibrosis at days 30 and 45, mediated by TGF-β1 activation. The increased COLV expression and associated inflammatory infiltrates observed in this model suggest that COLV contributes to pulmonary fibrosis progression.