Description:
<jats:p>We aimed to investigate the involvement of the nuclear receptor COUP‐TFII in the regulation of renin gene expression.</jats:p><jats:p>Protein‐DNA binding studies demonstrated that COUP‐TFII binds to the proxDR sequence in the proximal renin promoter. Knockdown of COUP‐TFII in the renin‐producing cell lines As4.1 and Calu‐6 reduced the stimulation of renin mRNA expression by cAMP agonists. The mutation of the proxDR element in renin promoter reporter gene constructs abrogated the inducibility by cAMP. The proxDR sequence was essential for the function of a renin promoter cAMP‐response element. Knockdown of COUP‐TFII or cAMP‐binding protein (CREB) decreased the basal renin gene expression. When CREB was knocked down, the deficiency of COUP‐TFII did not further diminish the renin expression. Mice deficient in COUP‐TFII have lower renin expression than their control strain. Surprisingly, there was no significant difference in both plasma renin concentration and blood pressure between wildtype and COUP‐TFII‐deficient mice. Altogether our data show that COUP‐TFII is involved in the control of renin gene expression. To better characterize the role of COUP‐TFII for the renin production in vivo we are generating mice with selective COUP‐TFII deletion in the renin‐producing cells of the kidney.</jats:p>