Control of renin [corrected] gene expression.

Renin, as part of the renin-angiotensin system, plays a critical role in the regulation of blood pressure, electrolyte homeostasis, mammalian renal development, and progression of fibrotic/hypertrophic diseases. Renin gene transcription is subject to complex developmental and tissue-specific regulation. Initial studies using the mouse As4.1 cell line, which has many characteristics of the renin-expressing juxtaglomerular cells of the kidney, have identified a proximal promoter region (-197 to -50 bp) and an enhancer (-2,866 to -2,625 bp) upstream of the Ren-1(c) gene, which are critical for renin gene expression. The proximal promoter region contains several transcription factor binding sites including a binding site for the products of the developmental control genes Hox. 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, all of which are known to alter renin mRNA levels. Furthermore, in vivo models have validated several of these key components found within the proximal promoter region and the enhancer as well as other key sites necessary for renin gene transcription.