Zhang Fang, Geng Yumei, Shi Xuefeng, Duo Jie
Suzhou Medical College of Soochow University, No.199 Renai Road, Suzhou Industrial Park, Suzhou 215123, People's Republic of China; Department of Respiratory and Critical Care Medicine, Qinghai Provincial People's Hospital, No.2 Gonghe Road, Chengdong District, Xining 810000, People's Republic of China.
Department of Respiratory and Critical Care Medicine, Qinghai Provincial People's Hospital, No.2 Gonghe Road, Chengdong District, Xining 810000, People's Republic of China.
Biochem Biophys Res Commun. 2025 May 12;763:151741. doi: 10.1016/j.bbrc.2025.151741. Epub 2025 Apr 1.
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.
慢性阻塞性肺疾病（COPD）以不可逆的气流受限为特征，缺乏有效的早期诊断和治疗策略。虽然气道炎症推动COPD进展，但其机制仍不清楚。早期生长反应蛋白3（EGR3）作为适应性免疫的调节因子，尚未在COPD相关炎症中进行研究。在此，我们使用香烟烟雾诱导的小鼠模型研究了EGR3在COPD发病机制中的作用。将EGR3基因敲除（EGR3-/-）小鼠和野生型小鼠暴露于烟雾中6个月。与野生型相比，EGR3-/-小鼠肺功能改善、气道阻力降低且肺泡结构损伤减轻。机制上，EGR3缺乏抑制了香烟烟雾诱导的肺组织和血清中TLR4/NF-κB信号通路的激活，并下调了TIMP-1的表达。本研究通过TLR4/NF-κB/TIMP-1轴将EGR3鉴定为COPD进展的新型促进因子，为COPD管理提供了潜在的生物标志物和治疗靶点。
