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• W4387568581 abstract "The dysregulation of local circadian clock has been implicated in the pathogenesis of a broad spectrum of diseases. However, the pathophysiological role of intrinsic circadian clocks Rev-Erbα in ischemia-reperfusion (IR)-induced acute lung injury (ALI) remains unclear.The IR-ALI model was established by subjecting isolated perfused rat lungs to 40 min of ischemia followed by 60 min of reperfusion. Rats were randomly assigned to one of six groups: control, control + SR9009 (Rev-Erbα agonist, 50 mg/kg), IR, and IR + SR9009 at one of three dosages (12.5, 25, 50 mg/kg). Bronchoalveolar lavage fluids (BALF) and lung tissues were obtained and analyzed. In vitro experiments utilized mouse lung epithelial cells (MLE-12) exposed to hypoxia-reoxygenation (HR) and pretreated with SR9009 (10 µM/L) and Rev-Erbα siRNA.SR9009 exhibited a dose-dependent reduction in lung edema in IR-ALI. It significantly inhibited the production of TNF-α, IL-6, and CINC-1 in BALF. Moreover, SR9009 treatment restored suppressed IκB-α levels and reduced nuclear NF-κB p65 levels in lung tissues. In addition, a SR9009 mitigated IR-induced apoptosis and mitogen-activated protein kinase (MAPK) activation in injured lung tissue. Finally, treatment with Rev-Erbα antagonist SR8278 abolished the protective action of SR9009. In vitro analyses showed that SR9009 attenuated NF-κB activation and KC/CXCL-1 levels in MLE-12 cells exposed to HR, and these effects were significantly abrogated by Rev-Erbα siRNA.The findings suggest that SR9009 exerts protective effects against IR-ALI in a Rev-Erbα-dependent manner. SR9009 may provide a novel adjuvant therapeutic approach for IR-ALI." @default.
• W4387568581 created "2023-10-13" @default.
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• W4387568581 date "2023-10-12" @default.
• W4387568581 modified "2023-10-15" @default.
• W4387568581 title "Targeting Rev-Erbα to protect against ischemia-reperfusion-induced acute lung injury in rats" @default.
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• W4387568581 doi "https://doi.org/10.1186/s12931-023-02547-7" @default.
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