Peroxisome proliferator-activated receptor-γ is involved in the control of renin gene expression

Based on the presence of a functional retinoic acid receptor/retinoid X receptor transcription factor binding sequence (hormone-responsive element) in the renin gene enhancer and on the fact that the peroxisome proliferator-activated receptors (PPARs) bind to DNA as heterodimers with retinoid X receptors, we speculated that PPARs are involved in the regulation of renin gene expression. To test this hypothesis, we used the human renin-producing cell line CaLu-6. Endogenous or pharmacological PPAR gamma agonists (unsaturated fatty acids and thiazolidinediones, respectively) stimulated renin gene expression. Surprisingly, we found that PPAR gamma targets a palindromic repeat with a 3-bp spacer (Pal3) in the proximal human renin promoter. Thus, renin is the first gene described with a functional Pal3 sequence. PPAR gamma agonists also stimulated renin gene expression in cultured native juxtaglomerular cells, which are the main source of renin in vivo. In summary, PPAR gamma was identified as a novel intracellular mediator involved in the upregulation of renin transcription.