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Table of Contents
Vol. 107, No. 2, 2007
Issue release date: October 2007
Section title: Original Paper
Nephron Physiol 2007;107:p35–p44
(DOI:10.1159/000106792)

Mechanistic Analysis of VDR-Mediated Renin Suppression

Nakane M. · Ma J. · Ruan X. · Kroeger P.E. · Wu-Wong R.
Abbott Laboratories, Abbott Park, Ill., USA

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: November 05, 2006
Accepted: May 08, 2007
Published online: August 08, 2007
Issue release date: October 2007

Number of Print Pages: 1
Number of Figures: 7
Number of Tables: 2

ISSN: (Print)
eISSN: 1660-2137 (Online)

For additional information: http://www.karger.com/NEP

Abstract

Background: The vitamin D receptor (VDR) is involved in the regulation of renin expression and vitamin D analogs down-regulated renin mRNA expression in As4.1 cells. Methods: Microarray analysis was used to assess the VDR-mediated gene expression profile in As4.1 cells treated with paricalcitol, followed by real-time RT-PCR. Mechanistic analyses were done using siRNA, electrophoretic mobility shift assay (EMSA) and Western blotting. Results: Microarray analysis shows that 709 target genes were affected by paricalcitol with 286 up- and 423 downregulated. A number of major pathways were impacted including transcription factors. Real-time RT-PCR confirmed the microarray results. Treatment of the cells with siRNA against nuclear receptor co-repressor (NCOR1) eliminated VDR-mediated renin suppression. Using EMSA, paricalcitol treatment reduced the level of protein complex binding to the cyclic AMP-responsive element (CRE)-like domain in the renin distal enhancer region. VDR, CRE-binding protein (CREB1) and NCOR1 were identified in the complex binding to the CRE-like domain by Western blot in the paricalcitol-treated cells. Paricalcitol treatment resulted in an increase in the VDR level, but no significant change in the CREB1 and NCOR1 levels. Conclusion: These results suggest that VDR-mediated renin suppression likely acts through a transcriptional regulatory complex including CREB1, NCOR1 and VDR that binds to the CRE-like domain in the renin enhancer region.

© 2007 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: November 05, 2006
Accepted: May 08, 2007
Published online: August 08, 2007
Issue release date: October 2007

Number of Print Pages: 1
Number of Figures: 7
Number of Tables: 2

ISSN: (Print)
eISSN: 1660-2137 (Online)

For additional information: http://www.karger.com/NEP


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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