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- W2885201575 abstract "Objective—Cardiovascular effects of angiotensin II are primarily mediated via the angiotensin II type 1 receptor (AT1R). Kruppel-like factor 4 (KLF4), a transcription factor that binds to the transforming growth factor (TGF)-β control element (TCE), regulates a variety of receptor expression in vascular smooth muscle cells. In the present study, we investigated the mechanisms of TGF-β-mediated KLF4 regulation of AT1R expression. Methods and Results—Coimmunoprecipitation, chromatin immunoprecipitation, and luciferase assays were performed, with the results suggesting that Sp1 forms a complex with KLF4 bound to the TCE of the AT1R promoter and cooperatively activates AT1R transcription in vascular smooth muscle cells under basal conditions. On activation of TGF-β1 signaling, Sp1 is dissociated from the KLF4-Sp1 complex through PKC-δ-mediated KLF4 phosphorylation at Thr401, downregulating AT1R expression. Simultaneously, TGF-β1 facilitates KLF4-PPAR–γ complex formation and its binding to the TCE of the AT1R ..." @default.
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- W2885201575 date "2012-04-01" @default.
- W2885201575 modified "2023-09-24" @default.
- W2885201575 title "TGF-β1 Downregulates AT1 Receptor Expression via PKC-δ-Mediated Sp1 Dissociation From KLF4 and Smad-Mediated PPAR-γ Association With KLF4" @default.
- W2885201575 hasPublicationYear "2012" @default.
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