Interstitial tonicity controls TonEBP expression in the renal medulla

Mee R. Sheen, Jeong Ah Kim, Sun W. Lim, Ju Y. Jung, Ki H. Han, Un S. Jeon, Soo H. Park, Jin Kim, H. Moo Kwon

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Cells in the hyperosmotic kidney medulla, express a transcriptional activator termed tonicity responsive enhancer binding protein (TonEBP). Genes targeted by TonEBP protect kidney cells from the deleterious effects of hyperosmolality by inducing the expression of organic osmolytes and molecular chaperones, and other genes that mediate urine concentration such as aquaporin-2 and urea transporters. We tested here the effect of hypertonicity and hyperosmotic salt in the renal medullary interstitium on the expression TonEBP. When massive water diuresis was induced in rats the medullary sodium concentrations did not change, neither did TonEBP expression. In these animals the medullary tonicity was unchanged despite the production of dilute urine. On the other hand, treatment with the loop diurectic furosemide resulted in a dose-dependent decrease in the medullary sodium concentration causing a reduction in interstitial tonicity. Here, TonEBP expression was blunted in the outer and inner medulla which was due, in part, to decreased mRNA abundance. As expected, the expression of TonEBP target genes in the renal medulla also decreased in response to furosemide. Hence TonEBP expression in the renal medulla is stimulated by interstitial hypertonicity.

Original languageEnglish
Pages (from-to)518-525
Number of pages8
JournalKidney International
Issue number5
StatePublished - Mar 2009

Bibliographical note

Funding Information:
We thank Jurgen Schnermann and Mark Knepper at NIH for the use of flame photometer. This work was supported by NIH grant DK42479. JAK and SWL were supported the National Kidney Foundation Fellowship.


  • Aldose reductase
  • Aldosterone
  • Furosemide
  • HSP70
  • Vasopressin
  • Water diuresis


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