Transcription Suppression of Thromboxane Receptor Gene Expression by Retinoids in Vascular Smooth Muscle Cells

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Author(s)

    • URUNO Akira
    • Division of Nephrology, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine
    • SUGAWARA Akira
    • Division of Nephrology, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine
    • KUDO Masataka
    • Division of Nephrology, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine
    • SATO Mayumi
    • Division of Nephrology, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine
    • SATO Kazunori
    • Division of Nephrology, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine
    • ITO Sadayoshi
    • Division of Nephrology, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine
    • TAKEUCHI Kazuhisa
    • Division of Nephrology, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine

Abstract

<B>Thromboxane (TX) A<SUB>2</SUB> induces contraction and proliferation of vascular smooth muscle cells (VSMCs) <I>via</I> its specific membrane TX receptor (TXR), possibly leading to the progression of atherosclerosis. Retinoids, derivatives of vitamin A, have recently been shown to be anti-atherosclerotic in VSMCs. We therefore examined the effects of retinoids on TX-induced cell growth and TXR expression in VSMCs. TX-induced VSMC proliferation assessed by <SUP>3</SUP>H-thymidine incorporation was completely abrogated by all-<I>trans</I> retinoic acid (ATRA) treatment. The expression of TXR mRNA was significantly decreased by treatment either with ATRA or its stereoisomer 9-<I>cis</I> retinoic acid (RA). Transcription activity of the TXR gene promoter was suppressed by treatment with these retinoids, and a study using retinoid receptor-selective agonists demonstrated that retinoic acid receptors (RARs), rather than retinoid X receptors (RXRs), were mainly involved in the transcription suppression. Deletion analyses demonstrated that the suppression was mediated <I>via</I> the -22/-7 GC-box related sequence. Electrophoretic mobility shift assays showed that Sp1, but not RAR and/or RXR, could bind to the element. The formation of the Sp1-DNA complex was inhibited by co-incubation with RAR, but not by RXR. Taken together, these findings suggest that TXR gene transcription suppression may be mediated by the inhibition of Sp1 binding to the -22/-7 GC-box related sequence by activated RAR, which may result in the inhibition of TX-induced VSMC proliferation. Our study indicates a novel anti-atherosclerotic action of retinoids in VSMCs. (<I>Hypertens Res</I> 2003; 26: 815-821)</B>

Journal

  • Hypertension Research

    Hypertension Research 26(10), 815-821, 2003-10-01

    The Japanese Society of Hypertension

References:  33

Cited by:  5

Codes

  • NII Article ID (NAID)
    10012457647
  • NII NACSIS-CAT ID (NCID)
    AA10847079
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    09169636
  • Data Source
    CJP  CJPref  J-STAGE 
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