Nuclear receptor LXRalpha is involved in cAMP-mediated human renin gene expression

Molecular and Cellular Endocrinology
Kouichi TamuraVictor J Dzau

Abstract

The cAMP-signaling pathway plays a crucial role in the regulation of the renin gene, but the mechanism involved remains poorly understood. We have focused our studies of renin gene regulation on the unique cAMP responsive element (huREN/CNRE, -135 to -107) in the human renin promoter. We have cloned a protein that binds to this unique CNRE and demonstrated that this protein is liver X receptor-alpha (LXRalpha), a transcriptional factor of the nuclear receptor family. Transient expression of LXRalpha in human renin-producing Calu-6 cells increased cAMP inducibility of human renin promoter. Similarly, LXRalpha-stably transfected Calu-6 cells exhibited increased cAMP inducibility of renin promoter as well as the endogenous renin gene. Site-directed mutation of huREN/CNRE, which disrupted LXRalpha binding, decreased cAMP-induced transcriptional activity of human renin promoter. Furthermore, we demonstrated that the binding of LXRalpha derived from human juxtaglomerular cells, the main production site of renin in the kidney, to the huREN/CNRE in vivo. These results suggest that LXRalpha plays an important role in the cAMP-mediated regulation of human renin gene transcription by binding to CNRE.

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Citations

Mar 23, 2011·Pflügers Archiv : European journal of physiology·Michael DeschVladimir T Todorov
May 12, 2012·Pflügers Archiv : European journal of physiology·Sean T GlennLi Pan
Dec 28, 2007·Molecular Pharmaceutics·Jeff L Staudinger, Kristin Lichti
Dec 14, 2007·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Xiyou Zhou, Curt D Sigmund
Jul 12, 2005·The Journal of Clinical Investigation·Fulvio MorelloVictor J Dzau
Mar 17, 2009·Conflict and Health·Birthe SteinerSandrine Rosenberger
Nov 28, 2008·Cardiovascular Therapeutics·Jerzy Bełtowski
Apr 16, 2010·Physiological Reviews·Hayo CastropCharlotte Wagner

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