Transcriptional Regulation of Renin

Abstract

Renin, as a component of the renin-angiotensin system, plays important roles in the regulation of blood pressure, electrolyte homeostasis, and mammalian renal development. Transcription of renin genes is subject to complex developmental and tissue-specific regulation. Progress has been made recently in elucidating the molecular mechanisms involved in renin gene expression. Using mouse As4.1 cells, which have many features characteristic of the renin-expressing juxtaglomerular cells of kidney, a proximal promoter region (−197 to −50 bp) and an enhancer (−2866 to −2625 bp) have been identified in the mouse renin gene, Ren-1 c , that are critical for its expression. The proximal promoter region contains at least 7 transcription factor-binding sites, including a binding site for the products of Hox , developmental control genes. The enhancer consists of at least 11 transcription factor-binding sites and is responsive to various signal transduction pathways, including cAMP, retinoic acid, endothelin-1, and cytokines, to alter renin mRNA levels. Sequence highly homologous to the mouse enhancer is also found in the human and rat renin genes. How these regulatory regions function in vivo will be the focus of future study.