Increased Renin Production in Mice With Deletion of Peroxisome Proliferator-Activated Receptor-γ in Juxtaglomerular Cells

被引：24

作者：

Desch, Michael ^{[1
]}

Schreiber, Andrea ^{[1
]}

Schweda, Frank ^{[1
]}

Madsen, Kirsten ^{[2
]}

Friis, Ulla G. ^{[2
]}

Weatherford, Eric T. ^{[3
,4
]}

Sigmund, Curt D. ^{[3
,4
]}

Lopez, Maria Luisa Sequeira ^{[5
]}

Gomez, R. Ariel ^{[5
]}

Todorov, Vladimir T. ^{[1
]}

机构：

[1] Univ Regensburg, Inst Physiol, D-93040 Regensburg, Germany

[2] Univ So Denmark, Inst Med Biol, Dept Physiol & Pharmacol, Odense, Denmark

[3] Univ Iowa, Dept Internal Med, Iowa City, IA USA

[4] Univ Iowa, Dept Mol Physiol & Biophys, Iowa City, IA USA

[5] Univ Virginia, Sch Med, Dept Pediat, Charlottesville, VA 22908 USA

来源：

HYPERTENSION | 2010年 / 55卷 / 03期

关键词：

basic science; gene expression/regulation; hypertension (kidney); renin; cell signaling; INDUCED FLUID RETENTION; INSULIN-RESISTANCE; BLOOD-PRESSURE; TRANSCRIPTIONAL REGULATION; EXPRESSION; AGONIST; MUSCLE; ADIPOGENESIS; HYPERTENSION; ANGIOTENSIN;

D O I：

10.1161/HYPERTENSIONAHA.109.138800

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

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.)

引用

页码：660 / 666

页数：7