Glucocorticoids inhibit transcription and expression of the UT-A urea transporter gene

American Journal of Physiology. Renal Physiology
Tao PengS M Bagnasco

Abstract

Dexamethasone treatment increases urea excretion and decreases urea permeability and urea transporter UT-A1 protein abundance in the inner medullary collecting duct (IMCD) of adrenalectomized rats. We examined the effect of dexamethasone treatment for 3 days on the abundance of several UT-A mRNA transcripts in rat renal medulla. By Northern blot analysis, a significant decrease in mRNA expression was observed in the inner medulla of dexamethasone-treated rats compared with controls for UT-A1 (71%), UT-A3 (75%), and UT-A3b (75%), but not for UT-A2. We then tested the effect of 100 nM dexamethasone on the activity of promoter I in the UT-A gene, using LLC-PK(1)-GR101 cells that express the glucocorticoid receptor. Dexamethasone significantly decreased the activity of rat UT-A promoter I (72%) but did not affect UT-A promoter II. Deletion analysis and site-directed mutagenesis demonstrated that sequences between -423 and -244 are important for this inhibition and that a 10-bp sequence at -363, which binds a nuclear protein in a gel shift assay, is necessary for basal promoter activity. The specific factors involved in repression of UT-A promoter I activity by glucocorticoids remain to be determined.

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Citations

Aug 11, 2005·American Journal of Physiology. Renal Physiology·Robert A FentonMark A Knepper
May 25, 2012·American Journal of Physiology. Renal Physiology·Louise C EvansMatthew A Bailey
Sep 26, 2012·Pflügers Archiv : European journal of physiology·Janet D KleinJeff M Sands
May 17, 2012·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Jeff M Sands
Feb 1, 2007·The Journal of Membrane Biology·R A FentonM A Knepper
Feb 1, 2007·The Journal of Membrane Biology·M D McDonaldP J Walsh
Feb 1, 2007·The Journal of Membrane Biology·C P Smith, R A Fenton
Nov 2, 2004·Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology·M D McDonaldP J Walsh
Jun 12, 2012·Respiratory Physiology & Neurobiology·M Danielle McDonaldPatrick J Walsh
Jul 12, 2011·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Tamara M RodelaPatrick J Walsh
Apr 1, 2011·British Journal of Pharmacology·Gavin Stewart
Jan 14, 2003·Annual Review of Physiology·Jeff M Sands
Dec 17, 2009·Seminars in Nephrology·Jeff M Sands
Aug 10, 2004·Current Opinion in Nephrology and Hypertension·Jeff M Sands
Sep 9, 2005·Journal of the American Society of Nephrology : JASN·Jørgen FrøkiaerMark A Knepper
Oct 22, 2002·American Journal of Physiology. Renal Physiology·Heddwen L BrooksMark A Knepper
Dec 11, 2002·American Journal of Physiology. Renal Physiology·Serena M Bagnasco
Feb 17, 2009·The Journal of Experimental Biology·M Danielle McDonaldPatrick J Walsh
Oct 25, 2002·Journal of the American Society of Nephrology : JASN·Jeff M Sands
Jul 1, 2006·The Journal of Experimental Biology·Tammy M Rodela, Patricia A Wright

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