Osmotic response element-binding protein (OREBP) is an essential regulator of the urine concentrating mechanism.
OREBP (osmotic response element-binding protein), also called TonEBP or NFAT5, is thought to induce the expression of genes that increase the accumulation of organic osmolytes to protect cells against a hypertonic environment. To investigate the consequences of lacking OREBP activity, transgenic (Tg) mice that overexpress OREBPdn (dominant negative form of OREBP) specifically in the epithelial cells of the renal collecting tubules were generated. These mice showed impairment in their urine concentrating mechanism, most likely due to reduced expression of the aquaporin AQP2 and the urea transporter UT-A1 and UT-A2 mRNAs. When deprived of water or after the administration of a vasopressin analogue, urine osmolality of the Tg mice was significantly increased but not to the same extent as that of the wild type mice. The expression of AQP2 and UT-A1, but not UT-A2 mRNAs, was increased to the same level as that of the wild type mice in the water deprivation state, indicating that the vasopressin regulatory mechanism was not affected by OREBPdn. These data indicate that in addition to vasopressin, OREBP is another essential regulator of the urine concentrating mechanism. Furthermore, the OREBPdn Tg mice developed progressive hydronephrosis soon after weaning, confirming the osmoprotective function of OREBP implicated by the in vitro experiments.
Lam
Amy K M
AK
Institute of Molecular Biology, The University of Hong Kong, Hong Kong Special Administrative Region, China.
Ko
Ben C B
BC
Tam
Sidney
S
Morris
Ryan
R
Yang
James Y
JY
Chung
Sookja K
SK
Chung
Stephen S M
SS
D000818:Animals; D051399:Aquaporin 2; D020346:Aquaporins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D007668:Kidney / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D007671:Kidney Concentrating Ability / Q000502:physiology; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D050778:NFATC Transcription Factors; D009997:Osmotic Pressure; D010641:Phenotype; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014556:Urine / Q000737:chemistry*; D014667:Vasopressins / Q000737:chemistry / Q000378:metabolism; D014867:Water / Q000008:administration & dosage / Q000378:metabolism; D000096982:Urea Transporters
D051399:Aquaporin 2; D020346:Aquaporins; D004268:DNA-Binding Proteins; D026901:Membrane Transport Proteins; D050778:NFATC Transcription Factors; D014157:Transcription Factors; D014667:Vasopressins; D014867:Water; D000096982:Urea Transporters; C496024:Aqp2 protein, mouse