Upregulation of urea transporter UT-A2 and water channels AQP2 and AQP3 in mice lacking urea transporter UT-B.
The UT-B urea transporter is the major urea transporter in red blood cells and kidney descending vasa recta. Humans and mice that lack UT-B have a mild urine-concentrating defect. Whether deletion of UT-B altered the expression of other transporter proteins involved in urinary concentration was tested. Fluorescence-based real-time reverse transcription-PCR and Northern blot analysis showed upregulation of the UT-A2 urea transporter and the aquaporin 2 (AQP2) and AQP3 water channel transcripts but no change in other urea transporters or AQP. Western blot analysis showed that UT-A2 protein abundance in the outer medulla of UT-B null mice increased to 122 +/- 6% of wild-type control. AQP2 protein abundance increased to 177 +/- 32% and 127 +/- 7% in the outer and inner medulla, respectively, of UT-B null versus wild-type mice. The abundance of UT-A1, AQP1, renal outer medullary potassium channel, and NKCC2/BSC1 proteins were not significantly different between UT-B null and wild-type mice. The increases in AQP2 and AQP3 would reduce water loss and improve concentrating ability. The lack of UT-B does not result in a change in expression of urea transporters involved in urea reabsorption from the inner medullary collecting duct (UT-A1 and UT-A3). However, UT-B null mice have a selective increase in UT-A2 protein abundance. This may be an adaptive response to the loss of UT-B, because UT-B and UT-A2 are involved in different intrarenal urea recycling pathways.
Klein
Janet D
JD
Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
Sands
Jeff M
JM
Qian
Liman
L
Wang
Xiaodan
X
Yang
Baoxue
B
D000818:Animals; D051399:Aquaporin 2; D051400:Aquaporin 3; D020346:Aquaporins / Q000235:genetics* / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D001835:Body Weight; D007668:Kidney / Q000033:anatomy & histology / Q000502:physiology; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D000096982:Urea Transporters
D051399:Aquaporin 2; D051400:Aquaporin 3; D020346:Aquaporins; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D000096982:Urea Transporters; C496024:Aqp2 protein, mouse; C496028:Aqp3 protein, mouse; C452857:urea transporter B, mouse