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

Tao Peng, Jeff M. Sands, Serena M. Bagnasco

Research output: Contribution to journalArticle

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-PK1-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.

Original languageEnglish (US)
Pages (from-to)F853-F858
JournalAmerican Journal of Physiology - Renal Physiology
Volume282
Issue number5 51-5
StatePublished - Jun 29 2002

Keywords

  • Kidney
  • Slc14a2 gene

ASJC Scopus subject areas

  • Physiology
  • Urology

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