Renin plays a key role in the regulation of blood pressure by catalyzing the limiting step in the generation of angiotensin II. The cAMP/PKA/CREB signaling cascade is the central intracellular mechanism that controls the expression of renin. cAMP targets cAMP Response Elements (CRE) in the renin gene promoter. Therefore we aimed to investigate the functional role of the human renin promoter CRE sequences in vivo. Three CRE sites are identified in the human renin promoter: proximal promoter CRE, proximal promoter CNRE (cAMP and overlapping negative response element) and distal enhancer CRE. Reporter gene studies in the human renin-producing Calu-6 cell line showed that the proximal CRE is dispensable for the cAMP-dependent stimulation of the human renin gene. Therefore we generated a transgenic mouse expressing a LacZ reporter under the control of the 12,2 kb human renin promoter containing mutations in the proximal CNRE and in the enhancer CRE. The proximal 12,2 kb human renin promoter is known to be sufficient for the cell-specific expression of renin gene. Beta-gal staining of adult kidney showed that the transgene is correctly targeted to the juxtaglomerular (JG) position of the afferent arterioles. Unexpectedly beta-gal was expressed also throughout the large arterial vessels as well as in glomeruli and in medullary interstitium of adult kidney.

Our data suggest that the human renin CRE regulatory sequences are important for the cell-specific expression of renin in the kidney.