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ERRgamma regulates cardiac, gastric, and renal potassium homeostasis.

Authors
  • Alaynick, William A
  • Way, James M
  • Wilson, Stephanie A
  • Benson, William G
  • Pei, Liming
  • Downes, Michael
  • Yu, Ruth
  • Jonker, Johan W
  • Holt, Jason A
  • Rajpal, Deepak K
  • Li, Hao
  • Stuart, Joan
  • McPherson, Ruth
  • Remlinger, Katja S
  • Chang, Ching-Yi
  • McDonnell, Donald P
  • Evans, Ronald M
  • Billin, Andrew N
Type
Published Article
Journal
Molecular Endocrinology
Publisher
The Endocrine Society
Publication Date
Feb 01, 2010
Volume
24
Issue
2
Pages
299–309
Identifiers
DOI: 10.1210/me.2009-0114
PMID: 19965931
Source
Medline
License
Unknown

Abstract

Energy production by oxidative metabolism in kidney, stomach, and heart, is primarily expended in establishing ion gradients to drive renal electrolyte homeostasis, gastric acid secretion, and cardiac muscle contraction, respectively. In addition to orchestrating transcriptional control of oxidative metabolism, the orphan nuclear receptor, estrogen-related receptor gamma (ERRgamma), coordinates expression of genes central to ion homeostasis in oxidative tissues. Renal, gastric, and cardiac tissues subjected to genomic analysis of expression in perinatal ERRgamma null mice revealed a characteristic dysregulation of genes involved in transport processes, exemplified by the voltage-gated potassium channel, Kcne2. Consistently, ERRgamma null animals die during the first 72 h of life with elevated serum potassium, reductions in key gastric acid production markers, and cardiac arrhythmia with prolonged QT intervals. In addition, we find altered expression of several genes associated with hypertension in ERRgamma null mice. These findings suggest a potential role for genetic polymorphisms at the ERRgamma locus and ERRgamma modulators in the etiology and treatment of renal, gastric, and cardiac dysfunction.

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