| First Author | Desch M | Year | 2010 |
| Journal | Mol Endocrinol | Volume | 24 |
| Issue | 11 | Pages | 2139-51 |
| PubMed ID | 20861226 | Mgi Jnum | J:182816 |
| Mgi Id | MGI:5316927 | Doi | 10.1210/me.2010-0134 |
| Citation | Desch M, et al. (2010) PPARgamma-dependent regulation of adenylate cyclase 6 amplifies the stimulatory effect of cAMP on renin gene expression. Mol Endocrinol 24(11):2139-51 |
| abstractText | The second messenger cAMP plays an important role in the regulation of renin gene expression. Nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma) is known to stimulate renin gene transcription acting through PPARgamma-binding sequences in renin promoter. We show now that activation of PPARgamma by unsaturated fatty acids or thiazolidinediones drastically augments the cAMP-dependent increase of renin mRNA in the human renin-producing cell line Calu-6. The underlying mechanism involves potentiation of agonist-induced cAMP increase and up-regulation of adenylate cyclase 6 (AC6) gene expression. We identified a palindromic element with a 3-bp spacer (Pal3) in AC6 intron 1 (AC6Pal3). AC6Pal3 bound PPARgamma and mediated trans-activation by PPARgamma agonist. AC6 knockdown decreased basal renin mRNA level and attenuated the maximal PPARgamma-dependent stimulation of the cAMP-induced renin gene expression. AC6Pal3 decoy oligonucleotide abrogated the PPARgamma-dependent potentiation of cAMP-induced renin gene expression. Treatment of mice with PPARgamma agonist increased AC6 mRNA kidney levels. Our data suggest that in addition to its direct effect on renin gene transcription, PPARgamma "sensitizes" renin gene to cAMP via trans-activation of AC6 gene. AC6 has been identified as PPARgamma target gene with a functional Pal3 sequence. |
