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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Tamura, K; Chen, YE; Tanaka, Y; Sakai, M; Tsurumi, Y; Koide, Y; Kihara, M; Pratt, RE; Horiuchi, M; Umemura, S; Dzau, VJ

Published Date

  • September 30, 2004

Published In

Volume / Issue

  • 224 / 1-2

Start / End Page

  • 11 - 20

PubMed ID

  • 15353176

International Standard Serial Number (ISSN)

  • 0303-7207

Digital Object Identifier (DOI)

  • 10.1016/j.mce.2004.07.005

Language

  • eng

Conference Location

  • Ireland