Unveiling the Role of PTCH1 in Airway Epithelial Repair Mechanisms in COPD Pathogenesis

<bold>Objective:</bold> This study aims to explore the expression pattern and biological role of PTCH1 in the lungs of patients with chronic obstructive pulmonary disease (COPD). <bold>Method:</bold> Three public datasets (GSE5058, GSE8545, and GSE10006) were utilized to investigate the expression pattern and associations of PTCH1 in COPD. Quantification of PTCH1 expression was carried out in lung tissue samples from COPD patients and healthy controls, as well as in mice with cigarette smoke-induced COPD. Manipulation of PTCH1 gene expression through overexpression and silencing techniques in the BEAS-2B airway epithelial cell line. <bold>Results:</bold> Significantly elevated PTCH1 expression was observed in the lung tissue and airway epithelium of COPD patients, COPD model mice, and CSE-treated BEAS-2B cells. PTCH1 expression was strongly associated with COPD development (OR=13.84, 95%CI=2.57-76.62), and the combination of PTCH1 expression with demographic factors could accurately predict COPD (AUC=0.841, 95%CI=0.769-0.913). In vitro experiments demonstrated that silencing PTCH1 expression reduced IL-6, IL-8, CCL2 expression, and ROS production, while enhancing cell proliferation and migration. Conversely, PTCH1 overexpression yielded opposing effects. Moreover, downregulation of PTCH1 led to increased OPA1 expression and reduced mitochondrial damage. <bold>Conclusion:</bold> PTCH1 plays a pivotal role in regulating repair mechanisms of airway epithelial cell damage in the context of COPD. A deeper understanding of how PTCH1 influences these processes could pave the way for potential therapeutic interventions in COPD management, ultimately enhancing patient outcomes.