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.

Qingke Pingchuan granules (QKPCG), a patented traditional Chinese medicine, clinically, are recommended for acute tracheobronchitis, cough, community-acquired pneumonia, and other respiratory diseases. However, its potential protective effect and mechanism of action in acute lung injury (ALI) have not been explored. We aimed to explore the mechanisms underlying the protective role of QKPCG in ALI. The therapeutic efficacy of QKPCG was investigated in a lipopolysaccharide (LPS)-induced ALI mouse model.Mice were divided into three groups, namely, the Control, LPS, and LPS + QKPCG groups. Mice in the LPS + QKPCG group were administered QKPCG intragastrically as a treatment once a day for a total of three days. QKPCG effectively increased survival and reduced lung injury in treated mice.It significantly reduced the LPS-induced expression of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), IL-1α, and IL-1β. RNA-sequencing followed by real-time quantitative polymerase chain reaction validation suggested a critical role of the secretoglobin family 1A member 1 (Scgb1a1) gene in

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