REGULATION OF CYCLIC ADENOSINE MONOPHOSPHATE RESPONSE ELEMENT BINDING PROTEIN ON RENIN EXPRESSION IN KIDNEY VIA COMPLEX CYCLIC ADENOSINE MONOPHOSPHATE RESPONSE ELEMENT-BINDING-PROTEIN-BINDING PROTEIN/P300 RECRUITMENT

摘要

Introduction: Renin synthesis and release is the rate-limiting step in the renin-angiotensin system, because cyclic adenosine monophosphate (cAMP) has been identified as dominant pathway for renin gene expression, and cAMP response element-binding protein (CREB) is found in the human and mouse renin promoter.This study aimed to evaluate the role of CREB in expression of the renin gene.Materials and Methods: We created conditional deletion of CREB in mice with low-sodium diet, specifically in renin cells of the kidney. To assess the effect of CREB on renin expression, immunostaining of renin was used in samples from wild-type mice and mice with gene knock-down of CREB. Cyclic AMP response element-binding-protein-binding protein (CBP) and p300 were measured in cultured renin cells of the mice, and RNA detection was done with real-time polymerase chain reaction.Results: With low-sodium diet, renin was expressed along the whole wall of the afferent glomerular arterioles in wild-type mice, while there was no increase or even decrease in renin expression in CREB-specific deletion mice; RNA level of renin in cultured cells decreased by 50% with single knock-down of CREB, CBP, or p300, and decreased 70% with triple knock-down of CREB, CBP, and p300.Conclusions: This study found that CREB was important for renin synthesis and the role of CREB can be achieved through the recruitment of co-activators CBP and p300.