Desch, Michael and Schreiber, Andrea and Schweda, Frank and Madsen, Kirsten and Friis, Ulla G. and Weatherford, Eric T. and Sigmund, Curt D. and Lopez, Maria Luisa Sequeira and Gomez, R. Ariel and Todorov, Vladimir T. (2010) Increased Renin Production in Mice With Deletion of Peroxisome Proliferator-Activated Receptor-gamma in Juxtaglomerular Cells. HYPERTENSION, 55 (3). pp. 660-666. ISSN 0194-911X, 1524-4563
Full text not available from this repository. (Request a copy)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.)
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INDUCED FLUID RETENTION; INSULIN-RESISTANCE; BLOOD-PRESSURE; TRANSCRIPTIONAL REGULATION; EXPRESSION; AGONIST; MUSCLE; ADIPOGENESIS; HYPERTENSION; ANGIOTENSIN; basic science; gene expression/regulation; hypertension (kidney); renin; cell signaling |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Frank Schweda |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Aug 2020 06:45 |
| Last Modified: | 05 Aug 2020 06:45 |
| URI: | https://pred.uni-regensburg.de/id/eprint/25076 |
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