1. Semaglutide ameliorates lipopolysaccharide-induced acute lung injury through inhibiting HDAC5-mediated activation of NF-κB signaling pathway.
- Author
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Jiang, Zeyu, Tan, Jinyi, Yuan, Yan, Shen, Jiang, and Chen, Yan
- Subjects
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LUNG injuries , *LIPOPOLYSACCHARIDES , *IN vitro studies , *INTERLEUKINS , *FLOW cytometry , *IN vivo studies , *ANTI-inflammatory agents , *ANIMAL experimentation , *WESTERN immunoblotting , *CELLULAR signal transduction , *TREATMENT effectiveness , *RATS , *ENZYME-linked immunosorbent assay , *TUMOR necrosis factors , *HISTONE deacetylase , *POLYMERASE chain reaction , *CHOLECYSTOKININ , *PHARMACODYNAMICS - Abstract
Background: As a life-threatening respiratory syndrome, acute lung injury (ALI) is characterized by uncontrollable inflammatory activities. Semaglutide (SEM) has been identified as an effective anti-inflammatory drug in a variety of diseases. This study intended to explore the functional effect and potential mechanisms of SEM in ALI. Methods: Lipopolysaccharide (LPS) was used to construct an in vivo ALI model based on Sprague-Dawley (SD) rats and an in vitro ALI model based on human pulmonary artery endothelial cells (HPAECs). Hematoxylin & eosin (H&E) staining and ELISA were applied to evaluate the histopathological changes in pulmonary tissues and detect TNF-α and IL-6 levels. RT-qPCR and Western blotting were used to measure gene and protein expressions in pulmonary tissues and cells. HPAEC viability and apoptosis were evaluated by CCK-8 method and flow cytometry methods. Results: Semaglutide pretreatment significantly mitigated pulmonary injury, reduced TNF-α and IL-6 production, and led to a decrease in cleaved caspase-3 level and an increase in Bcl-2 level, suggesting SEM could ameliorate LPS-induced ALI in rats. In vitro, SEM increased the proliferative capability and mitigated inflammation and apoptosis in LPS-stimulated HPAECs. In addition, SEM inhibited HDAC5-mediated NF-κB signaling pathway in HPAECs. HDAC5 overexpression or NF-κB signaling activation could partly impair SEM-mediated protective effects against LPS-induced damage to HPAECs. Conclusion: Semaglutide restrains LPS-induced ALI by inhibiting HDAC5/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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