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KMID : 1128320070050010028
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Electrolytes & Blood Pressure
2007 Volume.5 No. 1 p.28 ~ p.33
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Regulation of Urea Transporters by Tonicity-responsive Enhancer Binding Protein
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Jung Ju-Young
Kwon H. Moo
Kim Jim
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Abstract
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Urea accumulation in the renal inner medulla plays a key role in the maintenance of maximal urinary concentrating ability. Urea transport in the kidney is mediated by transporter proteins that include renal urea transporter (UT-A) and erythrocyte urea transporter (UT-B). UT-A1 and UT-A2 are produced from the same gene. There is an active tonicity-responsive enhancer (TonE) in the promoter of UT-A1, and the UT-A1 promoter is stimulated by hypertonicity via tonicity-responsive enhancer binding protein (TonEBP). The downregulation of UT-A2 raises the possibility that TonEBP also regulates its promoter. There is some evidence that TonEBP regulates expression of UT-A in vivo; (1) during the renal development of the urinary concentrating ability, expression of TonEBP precedes that of UT-A1; (2) in transgenic mice expressing a dominant negative form of TonEBP, expression of UT-A1 and UT-A2 is severely impaired; (3) in treatment with cyclosporine A, TonEBP was significantly downregulated after 28 days. This downregulation involves mRNA levels of UT-A2; (4) in hypokalemic animals, downregulation of TonEBP contributed to the down regulation of UT-A in the inner medulla. These data support tha t TonEBP directly contributes to the urinary concentration and renal urea recycling by the regulation of urea transporters.
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KEYWORD
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Tonicity-responsive enhancer binding protein, Urea transporters, Urine concentration
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