Taipei Medical University Institutional Repository:Item 987654321/3204
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    Title: PPAR{delta}-mediated p21/p27 induction via increased CBP nuclear translocation in beraprost-induced antiproliferation of murine aortic smooth muscle cells.
    Authors: 阮淑慧
    Sue YM;Chung CP;Lin H;Chou Y;Jen CY;Li HF;Chang CC;Juan SH
    Contributors: 醫學系生理學科
    Date: 2009
    Issue Date: 2009-08-24 10:45:00 (UTC+8)
    Relation: Am J Physiol Cell Physiol.(297):C321-9.
    Note: We previously showed that an increase in the peroxisome proliferator-activated receptor-delta (PPARdelta), together with subsequent induction of inducible nitric oxide synthase (iNOS) by beraprost (BPS), inhibits aortic smooth muscle cell proliferation. Herein, we delineated the mechanisms of the antiproliferative effects of BPS through the induction of p21/p27. BPS concentration dependently induced the p21/p27 promoter- and consensus cAMP-responsive element (CRE)-driven luciferase activities, which were significantly suppressed by blocking PPARdelta activation. Surprisingly, other than altering the CRE-binding protein (CREB), BPS-mediated PPARdelta activation increased nuclear localization of the CREB-binding protein (CBP), a coactivator, which was further confirmed by chromatin immunoprecipitation. Furthermore, novel functional PPAR-responsive elements (PPREs) next to CREs in the rat p21/p27 promoter regions were identified, where PPARdelta interacted with CREB through CBP recruitment. BPS-mediated suppression of restenosis in mice with angioplasty was associated with p21/p27 induction. Herein, we demonstrate for the first time that BPS-mediated PPARdelta activation enhances transcriptional activation of p21/p27 by increasing CBP nuclear translocation, which contributes to the vasoprotective action of BPS.
    Data Type: article
    Appears in Collections:[Department of Physiology] Periodical Article

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