SKP2-Promoted Ubiquitination of FOXO3 Promotes the Development of Asthma

Abstract Asthma is a respiratory disease with dramatically increasing incidence globally. The present study explored the roles of S-phase kinase-associated protein 2 (SKP2) and forkhead box O3 (FOXO3) in asthma their involvement Krüppel-like factor 15–lipoprotein receptor-related 5 (KLF15–LRP5) axis. SKP2 expression patients OVA-induced asthmatic Sprague Dawley rats was detected by reverse transcription quantitative PCR Western blot assays. Alterations LRP5 were evaluated rats, followed measurement inflammatory cytokines using ELISA airway resistance methacholine challenge test. We applied TGF-β1 to establish smooth muscle cell (ASMC) proliferation model asthma. FOXO3 ubiquitination changes biological behaviors immunoprecipitation, MTT, Annexin V/propidium iodide Flow cytometry adopted detect cycle, used measure concentrations IL-4, IL-5, IL-13, IgE rat bronchoalveolar lavage fluid. highly expressed poorly rats. silencing decreased fluid, whereas enhanced upregulate KLF15, which bound promoter TGF-β1–induced ASMCs increased expression. hyperresponsiveness inflammation augmented ASMC inhibiting FOXO3/KLF15/LRP5 Additionally, overexpressed resulted reduced numbers G1 phase but G2/M phase. Collectively, we show that promotes suppress KLF15-LRP5 axis, thereby exacerbating