Journal article
Increased Renin Production in Mice With Deletion of Peroxisome Proliferator-Activated Receptor-gamma in Juxtaglomerular Cells
Hypertension (Dallas, Tex. 1979), Vol.55(3), pp.660-666
03/01/2010
DOI: 10.1161/HYPERTENSIONAHA.109.138800
PMCID: PMC2907524
PMID: 20065157
Abstract
We recently found that endogenous (free fatty acids) and pharmacological (thiazolidinediones) agonists of nuclear receptor Peroxisome proliferator-activated receptor (PPAR)gamma stimulate renin transcription. In addition, the renin gene was identified as a direct target of PPAR gamma. The mouse renin gene is regulated by PPAR gamma through a distal enhancer direct repeat closely related to consensus PPAR response element (PPRE). In vitro studies demonstrated that PPAR gamma knockdown stimulated PPRE-driven transcription. These data predicted that deficiency of PPAR gamma would upregulate mouse renin expression. Consistent with these observations knockdown of PPAR gamma increased the transcription of a reporter gene driven by the mouse renin PPRE-like motif in vitro. To study the impact of PPAR gamma on renin production in vivo, we used a cre/lox system to generate double-transgenic mice with disrupted PPAR gamma locus in renin-producing juxtaglomerular (JG) cells of the kidney (RC-PPAR gamma(fl/fl) mice). We provide evidence that PPAR gamma expression was effectively reduced in JG cells of RC-PPAR gamma(fl/fl) mice. Fluorescent immunohistochemistry showed stronger renin signal in RC-PPAR gamma(fl/fl) than in littermate control RC-PPAR gamma(wt/wt) mice. Renin mRNA levels and plasma renin concentration in RC-PPAR gamma(fl/fl) mice were almost 2-fold higher than in littermate controls. Arterial blood pressure and pressure control of renal vascular resistance, which play decisive roles in the regulation of renin production were indistinguishable between RC-PPAR gamma(wt/wt) and RC-PPAR gamma(fl/fl) mice. These data demonstrate that the JG-specific PPAR gamma deficiency results in increased mouse renin expression in vivo thus corroborating earlier in vitro results. PPAR gamma appears to be a relevant transcription factor for the control of renin gene in JG cells. (Hypertension. 2010; 55: 660-666.)
Details
- Title: Subtitle
- Increased Renin Production in Mice With Deletion of Peroxisome Proliferator-Activated Receptor-gamma in Juxtaglomerular Cells
- Creators
- Michael Desch - University of RegensburgAndrea Schreiber - University of RegensburgFrank Schweda - University of RegensburgKirsten Madsen - University of Southern DenmarkUlla G. Friis - University of Southern DenmarkEric T. Weatherford - Univ Iowa, Dept Internal Med, Iowa City, IA USACurt D. Sigmund - Univ Iowa, Dept Internal Med, Iowa City, IA USAMaria Luisa Sequeira Lopez - University of VirginiaR. Ariel Gomez - University of VirginiaVladimir T. Todorov - University of Regensburg
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.55(3), pp.660-666
- Publisher
- Lippincott Williams & Wilkins
- DOI
- 10.1161/HYPERTENSIONAHA.109.138800
- PMID
- 20065157
- PMCID
- PMC2907524
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Number of pages
- 7
- Grant note
- R37HL048058 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) Deutsche Forschungsgemeinschaft; German Research Foundation (DFG) K08DK075481 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) Sonderforschungsbereich 699
- Language
- English
- Date published
- 03/01/2010
- Academic Unit
- Molecular Physiology and Biophysics; Neuroscience and Pharmacology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984359810202771
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