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1 Department of Pathology and 2 Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322
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.
Slc14a2 gene; kidney
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