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Increased Renin Production in Mice With Deletion of Peroxisome Proliferator-Activated Receptor-γ in Juxtaglomerular Cells
| Content Provider | Scilit |
|---|---|
| Author | Desch, Michael Schreiber, Andrea Schweda, Frank Madsen, Kirsten Friis, Ulla G. Weatherford, Eric T. Sigmund, Curt D. Lopez, Maria Luisa Sequeira Gomez, R. Ariel Todorov, Vladimir T. |
| Copyright Year | 2010 |
| Description | Journal: Hypertension We recently found that endogenous (free fatty acids) and pharmacological (thiazolidinediones) agonists of nuclear receptor Peroxisome proliferator-activated receptor (PPAR)γ stimulate renin transcription. In addition, the renin gene was identified as a direct target of PPARγ. The mouse renin gene is regulated by PPARγ through a distal enhancer direct repeat closely related to consensus PPAR response element (PPRE). In vitro studies demonstrated that PPARγ knockdown stimulated PPRE-driven transcription. These data predicted that deficiency of PPARγ would upregulate mouse renin expression. Consistent with these observations knockdown of PPARγ increased the transcription of a reporter gene driven by the mouse renin PPRE-like motif in vitro. To study the impact of PPARγ on renin production in vivo, we used a cre/lox system to generate double-transgenic mice with disrupted PPARγ locus in renin-producing juxtaglomerular (JG) cells of the kidney (RC-PPARγ$ ^{fl/fl}$ mice). We provide evidence that PPARγ expression was effectively reduced in JG cells of RC-PPARγ$ ^{fl/fl}$ mice. Fluorescent immunohistochemistry showed stronger renin signal in RC-PPARγ$ ^{fl/fl}$ than in littermate control RC-PPARγ$ ^{wt/wt}$ mice. Renin mRNA levels and plasma renin concentration in RC-PPARγ$ ^{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-PPARγ$ ^{wt/wt}$ and RC-PPARγ$ ^{fl/fl}$ mice. These data demonstrate that the JG-specific PPARγ deficiency results in increased mouse renin expression in vivo thus corroborating earlier in vitro results. PPARγ appears to be a relevant transcription factor for the control of renin gene in JG cells. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907524/pdf https://core.ac.uk/download/pdf/50671085.pdf https://www.ahajournals.org/doi/pdf/10.1161/HYPERTENSIONAHA.109.138800 |
| Ending Page | 666 |
| Page Count | 7 |
| Starting Page | 660 |
| ISSN | 0194911X |
| e-ISSN | 15244563 |
| DOI | 10.1161/hypertensionaha.109.138800 |
| Journal | Hypertension |
| Issue Number | 3 |
| Volume Number | 55 |
| Language | English |
| Publisher | Ovid Technologies (Wolters Kluwer Health) |
| Publisher Date | 2010-03-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Hypertension Peripheral Vascular Disease Hypertension (kidney) Gene Expression/regulation Basic Science Cell Signaling |
| Content Type | Text |
| Resource Type | Article |
| Subject | Internal Medicine |
