Urea promotes TonEBP expression and cellular adaptation in extreme hypertonicity.
The transcriptional activator TonEBP is a central regulator of osmolality in the renal medulla and whole body water homeostasis. In order to understand the regulation of TonEBP in the renal medulla, we examined MDCK cells, a kidney-derived epithelial cell line, under conditions mimicking the renal medulla. Moderate changes in ambient tonicity, which was tolerated without prior adaptation, displayed lasting effects on TonEBP in bidirectional manner-stimulated by hypertonicity and inhibited by hypotonicity. TonEBP expression was further enhanced by extreme hypertonicity observed in the inner medullae of antidiuretic animals. Urea stimulated TonEBP expression and promoted cellular proliferation under the conditions of extreme hypertonicity. On the other hand, the TonEBP activity was negatively modulated under these conditions presumably to temper the highly abundant TonEBP. We conclude that urea is critical to the cellular adaptation to extreme hypertonicity and the high level of TonEBP expression in the inner medulla.
Kwon
Min Seong
MS
Department of Medicine, University of Maryland, 655 West Baltimore Street, Bressler 8029, Baltimore, MD 21201, USA.
Na
Ki Young
KY
Moeckel
Gilbert
G
Lee
Sang Do
SD
Kwon
H Moo
HM
D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D001622:Betaine / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006982:Hypertonic Solutions; D007038:Hypotonic Solutions; D007150:Immunohistochemistry; D007679:Kidney Medulla / Q000166:cytology / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000096:biosynthesis*; D009994:Osmolar Concentration; D014508:Urea / Q000378:metabolism*; D014882:Water-Electrolyte Balance / Q000502:physiology*
D006360:Heat-Shock Proteins; D006982:Hypertonic Solutions; D007038:Hypotonic Solutions; D050778:NFATC Transcription Factors; D001622:Betaine; D014508:Urea