Study on the changes of extracellular matrix morphology and components in COPD animal model by using lung decellularized scaffold.

Airway remodeling is a critical pathological process that influences the progression of chronic obstructive pulmonary disease(COPD). To better study small airway remodeling in COPD, we employed advanced techniques such as decellularized scaffolds, immunofluorescence, scanning electron microscopy, and proteomics to analyze morphological and compositional changes in the extracellular matrix (ECM). Our study revealed significant ultrastructural abnormalities in the decellularized scaffolds from the COPD group, including thinning of alveolar septa, enlargement of alveolar spaces, and fusion of multiple alveoli. Additionally, the ECM composition in the COPD group exhibited notable changes characterized by an increase in collagen fibers, type I and IV collagens, fibronectin, and laminin (p < .05), along with a decrease in elastin and glycosaminoglycans (p < .05). Proteomic analysis identified 70 differentially expressed proteins between the COPD group and the control group. These included 34 upregulated proteins such as Smarca2, Skt, Acvrl1, Myl2 (all with ratios >10.64), and 36 downregulated proteins such as Col6a6, Col6a5, and AnK3 (all with ratios <0.27). Pathway analysis indicated that activation of apoptosis (Enrichment Score, ES = 0.23) and epithelial-mesenchymal transition (ES = 0.38) genes and inhibition of collagen synthesis (ES = -0.43) and degradation (ES = -0.63) genes were observed in the COPD group. These findings enhance our understanding of the mechanisms underlying airway remodeling and provide a scientific basis for developing novel therapeutic strategies for COPD.