EGR3 deficiency alleviates cigarette smoke-induced pulmonary inflammation in COPD through TLR4/NF-κB/TIMP-1 axis

Chronic obstructive pulmonary disease (COPD), characterized by irreversible airflow limitation, lacks effective early diagnostic and therapeutic strategies. While airway inflammation drives COPD progression, its mechanisms remain unclear. Early growth response protein 3 (EGR3), a regulator of adaptive immunity, has not been explored in COPD-related inflammation. Here, we investigated EGR3's role in COPD pathogenesis using a cigarette smoke-induced murine model. EGR3 knockout (EGR3^-/-) and wild-type mice were exposed to smoke for 6 months. EGR3^-/- mice exhibited improved lung function, reduced airway resistance, and attenuated alveolar structural damage compared to wild-type. Mechanistically, EGR3 deficiency suppressed cigarette smoke-induced activation of the TLR4/NF-κB pathway and downregulated TIMP-1 expression in lung tissues and serum. This study identifies EGR3 as a novel promoter of COPD progression via the TLR4/NF-κB/TIMP-1 axis, offering a potential biomarker and therapeutic target for COPD management.