Peroxisome proliferator-activated receptor-gamma 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 PPARgamma agonists (unsaturated fatty acids and thiazolidinediones, respectively) stimulated renin gene expression. Surprisingly, we found that PPARgamma 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. PPARgamma agonists also stimulated renin gene expression in cultured native juxtaglomerular cells, which are the main source of renin in vivo. In summary, PPARgamma was identified as a novel intracellular mediator involved in the upregulation of renin transcription.
Todorov
Vladimir T
VT
Institute of Physiology, University of Regensburg, D-93040 Regensburg, Germany. vladimir.todorov@vkl.uni-regensburg.de
Desch
Michael
M
Schmitt-Nilson
Nina
N
Todorova
Anelia
A
Kurtz
Armin
A
D000813:Anilides / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D018014:Gene Transfer Techniques; D006801:Humans; D019787:Linoleic Acid / Q000494:pharmacology; D051379:Mice; D016297:Mutagenesis, Site-Directed; D019301:Oleic Acid / Q000494:pharmacology; D047495:PPAR gamma / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D012083:Renin / Q000096:biosynthesis* / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D045162:Thiazolidinediones / Q000494:pharmacology