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

Am J Physiol Renal Physiol. 2002 May;282(5):F853-8. doi: 10.1152/ajprenal.00262.2001.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Northern
  • Carrier Proteins / genetics*
  • Dexamethasone / pharmacology
  • Gene Deletion
  • Gene Expression / drug effects*
  • Glucocorticoids / pharmacology*
  • Kidney Medulla / chemistry
  • Kidney Medulla / metabolism*
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Transport Proteins / genetics*
  • Mutagenesis, Site-Directed
  • Promoter Regions, Genetic
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Transcription, Genetic / drug effects

Substances

  • Carrier Proteins
  • Glucocorticoids
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • RNA, Messenger
  • urea transporter
  • Dexamethasone