Electrolyte Blood Press.  2007 Jun;5(1):28-33. 10.5049/EBP.2007.5.1.28.

Regulation of Urea Transporters by Tonicity-responsive Enhancer Binding Protein

• Jung JY
• Kwon M
• Kim J

• KMID: 2134802
• DOI: http://doi.org/10.5049/EBP.2007.5.1.28

Abstract

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 that TonEBP directly contributes to the urinary concentration and renal urea recycling by the regulation of urea transporters.

MeSH Terms

Animals
Carrier Proteins*
Cyclosporine
Down-Regulation
Erythrocytes
Kidney
Mice
Mice, Transgenic
Recycling
RNA, Messenger
Urea*
Carrier Proteins
Cyclosporine
RNA, Messenger
Urea

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