Therapeutic Effect of Semaglutide on Pulmonary Function and Fibrosis in a Bleomycin-Induced and Spirometry-Confirmed Mouse Model of IPF

Feigh, Michael; Oró, Denise; Arraut, A.M.; Petersen, A.G.

doi:10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a4719

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“…14 Besides, SEM exhibits anti-inflammatory and protective effects on LPS-induced H9c2 cells. 15 Furthermore, SEM also exerts protective effects against Bleomycin-induced idiopathic pulmonary fibrosis, 16 implying its role in reviving pulmonary function. Therefore, it was suggested that SEM could play a therapeutic role in LPS-induced ALI.…”

Section: Introductionmentioning

confidence: 99%

Semaglutide ameliorates lipopolysaccharide-induced acute lung injury through inhibiting HDAC5-mediated activation of NF-κB signaling pathway

et al. 2022

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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.

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Section: Introductionmentioning

confidence: 99%