期刊
INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE
卷 16, 期 -, 页码 2817-2832出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/COPD.S328313
关键词
cigarette smoke; GLIPR1; PLAU; pyroptosis; chronic obstructive pulmonary disease
资金
- National Natural Science Foundation of China [81770039, 82070045]
- Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission [18140904002]
- National key RD plan [2016YFC1304104]
- Science and Technology Commission of Shanghai Municipality [20DZ2254400, 20XD1401200, 20DZ2261200]
- Zhongshan Hospital Clinical Research Foundation [2019ZSGG15]
- Shanghai Municipal Key Clinical Specialty [shslczdzk02201]
GLIPR1 plays a pivotal role in the pathogenesis of COPD and protects against the inflammatory response and airway damage induced by cigarette smoke exposure.
Background: Chronic obstructive pulmonary disease (COPD) is a major health problem associated with high mortality worldwide. Cigarette smoke (CS) exposure is the main cause of COPD. Glioma pathogenesis-related protein 1 (GLIPR1) plays a key role in cell growth, proliferation, and invasion; however, the role of GLIPR1 in COPD remains unclear. Methods: To clarify the involvement of GLIPR1 in COPD pathogenesis, Glipr1 knockout (Glipr1-/-) mice were generated. Wild-type (WT) and Glipr1-/-mice were challenged with CS for 3 months. To illustrate how GLIPR1 regulates CS-induced airway damage, knock-down experiments targeting GLIPR1 and PLAU, as well as overexpression experiments of PLAU, were performed with human bronchial epithelial cells. Results: Compared with WT mice, Glipr1-/-mice showed exacerbated CS-induced airway damage including lung inflammation, airway wall thickening, and alveolar destruction. After CS exposure, total proteins, total white cells, neutrophils, lymphocytes, IL-6, and matrix metalloproteinase-9 increased significantly in lung of Glipr1-/-mice than those in lung of WT mice. Furthermore, in vivo and in vitro experiments demonstrated that silencing of GLIPR1 inactivated PLAU/EGFR signaling and promoted caspase-1-dependent pyroptosis (a mode of inflammatory cell death) induced by CS and CS extract exposure, respectively. In vitro experiments further revealed the interaction between GLIPR1 and PLAU, and silencing of PLAU blocked EGFR signaling and promoted pyroptosis, while overexpression of PLAU activated EGFR signaling and reversed pyroptosis. Conclusion: To conclude, GLIPR1 played a pivotal role in COPD pathogenesis and protected against CS-induced inflammatory response and airway damage, including cell pyroptosis, through the PLAU/EGFR signaling. Thus, GLIPR1 may play a potential role in COPD treatment.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据