Dataset Information

GLIPR1 Protects Against Cigarette Smoke-Induced Airway Inflammation via PLAU/EGFR Signaling.

ABSTRACT:

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, knockdown 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.

SUBMITTER: Peng W

PROVIDER: S-EPMC8517531 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

GLIPR1 Protects Against Cigarette Smoke-Induced Airway Inflammation via PLAU/EGFR Signaling.

Peng Wenjun W Wu Yuanyuan Y Zhang Ge G Zhu Wensi W Chang Meijia M Rouzi Ainiwaer A Jiang Weipeng W Tong Lin L Wang Qin Q Liu Jie J Song Yuanlin Y Li Huayin H Li Ka K Zhou Jian J

International journal of chronic obstructive pulmonary disease 20211008

<h4>Background</h4>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.<h4>Methods</h4>To clarify the involvement of GLIPR1 in COPD pathogenesis, Glipr1 knockout (Glipr1-/-) mice were generated. Wild-type (WT) and Glipr1- ...[more]

PMID: 34675506

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Dataset Information

GLIPR1 Protects Against Cigarette Smoke-Induced Airway Inflammation via PLAU/EGFR Signaling.

Background

Methods

Results

Conclusion

Publications

GLIPR1 Protects Against Cigarette Smoke-Induced Airway Inflammation via PLAU/EGFR Signaling.

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