We found recently that activation of nuclear receptor PPARg stimulates renin gene transcription. PPARg targets different cis-acting regulatory elements in human and mouse renin genes. A proximal promoter palindrome (Pal3) is the main PPARg binding sequence in human renin gene. In contrast, mouse renin gene is regulated by PPARg through a distal enhancer direct repeat sequence closely related to the consensus PPAR Response Element (PPRE). In vitro studies demonstrated that PPARg deficiency decreased the Pal3-driven transcription and paradoxically increased PPRE-driven transcription. These data suggest that the deficiency of PPARg should decrease human, but increase mouse renin gene expression. To study the impact of PPARg on renin production in vivo we used the CRE/loxP system to generate a double transgenic mouse with disrupted PPARg gene in the renin-producing juxtaglomerular (JG) cells of the kidney (RenPGKO mouse). There were no signs of recombination of the PPARg floxed allele in extrarenal tissues of the RenPGKO mouse. PPARg expression in RenPGKO kidney preparations enriched of JG cells was sharply diminished as compared to littermate controls (LC). PPARg protein was decreased also in RenPGKO whole kidney extracts as compared to LC suggesting recombination not only in JG cells which account for less than 1% of all kidney cells. This finding is in line with earlier data showing that renin gene is developmentally active in renal arterial vessels and in collecting ducts which express PPARg. Fluorescent immunohistochemistry showed stronger renin signal in RenPGKOs than in LCs. Accordingly plasma renin concentration (PRC) in RenPGKOs was two fold higher than in LCs.

These data demonstrate that the kidney-specific PPARg deficiency results in increased mouse renin expression thus supporting the earlier in vitro results.