Identification of nuclear receptors that regulate renin gene expression

Renin (REN) expression is required to maintain blood pressure and electrolyte homeostasis. However, the mechanisms by which REN is transcriptionally regulated remain elusive. We reported a functional role for several nuclear receptors (NRs) on REN gene transcription. To identify other candidate NRs that regulate REN, we analyzed a publicly available microarray dataset (GUDMAP Developing Kidney ST1) to compare the expression pattern of REN and the 48 NRs across different kidney cell types. Our analysis revealed 14 NRs exhibiting a similar pattern as REN. We hypothesized that these NRs are co-regulated with REN and can regulate REN transcription. To test this hypothesis, we set up 2 cohorts of mice in which REN expression was either high or low compared to control mice and measured expression of REN and NRs in renal cortex by qPCR. The high-REN cohort was given the ACE inhibitor captopril (100g/kg/day) for 10 days, and the low-REN group was implanted subcutaneously with a deoxycorticosterone acetate pellet (50mg) and received 0.15 M NaCl in drinking water for 21 days (DOCA-salt) in addition to water. Captopril increased REN and reduced NR2F6 expression relative to vehicle treatment (REN: 16±1, p