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
Background Chronic obstructive pulmonary disease (COPD), a chronic inflammatory lung disease, is a leading cause of morbidity and mortality worldwide. Prolonged cigarette smoking (CS) that causes irreversible airway remodeling and significantly reduces lung function is a major risk factor for COPD. Kertin15+ (Krt15+) cells with the potential of self-renewal and differentiation properties have been implicated in the maintenance, proliferation, and differentiation of airway basal cells; however, the role of Krt15 in COPD is not clear.Methods Krt15 knockout (Krt15−/−) and wild-type (WT) mice of C57BL/6 background were exposed to CS for six months to establish COPD models. Krt15-Cre;Rosa26-tdTomato mice were used to trace the fate of the Krt15+ cells. Hematoxylin and eosin (H&E) and Masson stainings were performed to assess histopathology and fibrosis, respectively. Furthermore, lentivirus-delivered short hairpin RNA (shRNA) was used to knock down KRT15 in human bronchial epithelial (HBE) cells stimulated with cigarette smoke extract (CSE). The protein expression was assessed using western blotting, immunohistochemistry, and enzyme-linked immunosorbent assay.Results Krt15−/− CS mice developed severe inflammatory cell infiltration, airway remodeling, and emphysema. Moreover, Krt15 knockout aggravated CS-induced secretion of matrix metalloproteinase-9 (MMP-9) and epithelial-mesenchymal transformation (EMT). Consistent with this finding, KRT15 knockdown promoted MMP-9 expression and EMT progression in vitro, which was reversed by SB-3CT, an MMP-9 inhibitor. Furthermore, Krt15+ cells gradually increased in the bronchial epithelial cells during CS exposure in mice.Conclusion Krt15 regulates the EMT process by promoting MMP-9 expression and protects the lung tissue from CS-induced injury, inflammatory infiltration, and apoptosis. These results suggest Krt15 as a potential therapeutic target for COPD.
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