Purpose: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow limitation, largely driven by airway remodeling. Epithelial-mesenchymal transition (EMT) is a key mechanism underlying this process. Laminin subunit gamma-2 (LAMC2) is implicated in fibrosis and EMT, but its role in COPD-associated airway remodeling remains unclear. Methods: Differential expression analysis was performed using airway epithelial cell datasets from COPD patients and TGF-β 1-induced EMT models. Findings were validated in COPD patient lung tissues, smoke-exposed mice, and in vitro experiments. In vivo, chronic smoke-exposed mice were pre-treated intratracheally with adeno-associated virus (AAV)-shLAMC2. Functional assays involved siRNA knockdown or plasmid overexpression of LAMC2 in bronchial epithelial cells. RNA sequencing and pathway analyses were conducted to explore underlying mechanisms. Results: LAMC2 was significantly upregulated in COPD patient and murine airway epithelia. AAV-shLAMC2 administration alleviated airway remodeling and restored epithelial E-cadherin while reducing mesenchymal markers (N-cadherin, fibronectin), indicating attenuation of EMT. In vitro, LAMC2 was upregulated in TGF-β 1-stimulated epithelial cells, and its modulation significantly influenced EMT progression. Transcriptomic analysis suggested that AKT signaling as a potential downstream of LAMC2, supported by functional assays. Conclusion: LAMC2 is upregulated in COPD airway epithelium and promotes airway remodeling by regulating EMT, potentially through AKT signaling. These findings suggest that targeting LAMC2 may represent a potential strategy for mitigating COPD-associated airway remodeling. Keywords: COPD, airway remodeling, EMT, LAMC2
Wang et al. (Sun,) studied this question.