Interstitial tonicity controls TonEBP expression in the renal medulla.
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.
Sheen
Mee R
MR
Department of Medicine, University of Maryland, Baltimore, Maryland 21201,, USA.
Kim
Jeong-Ah
JA
Lim
Sun W
SW
Jung
Ju-Y
JY
Han
Ki-H
KH
Jeon
Un S
US
Park
Soo-H
SH
Kim
Jin
J
Kwon
H Moo
HM
D000818:Animals; D005665:Furosemide / Q000494:pharmacology; D007679:Kidney Medulla / Q000378:metabolism*; D008297:Male; D050778:NFATC Transcription Factors / Q000235:genetics*; D009997:Osmotic Pressure; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012492:Salts / Q000494:pharmacology; D012964:Sodium / Q000032:analysis
D050778:NFATC Transcription Factors; D012333:RNA, Messenger; D012492:Salts; D005665:Furosemide; D012964:Sodium