Upregulation of Urea Transporter UT-A2 and Water Channels AQP2 and AQP3 in Mice Lacking Urea Transporter UT-B
| Title: | Upregulation of Urea Transporter UT-A2 and Water Channels AQP2 and AQP3 in Mice Lacking Urea Transporter UT-B |
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| Authors: | Klein, MD, PhD, Janet; Sands, Jeff M.; Qian, Liman; Wang, MD, Xiaodan; Yang, Baoxue |
| Publisher: | Journal of American Society of Nephrology |
| Date Published: | May 01, 2004 |
| Reference Number: | 682 |
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.
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This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
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Humans and mice lacking UT-B are less able to concentrate urine than normal, though this defect is classified as mild, not severe. It is thought that the lack of UT-B results in an inability to concentrate urea due to an impaired ability to exchange urea between the ascending and descending vasa recta in the kidney. This defect should produce a more severe inability to concentrate urine than observed. Klein, et al., conducted a series of experiments on mice bred to lack UT-B to see if any compensating action occurs to reduce the extent of the urine concentrating defect.
The research team observed that both the number of UT-A2, AQP2 and AQP3 proteins and the mRNA that helps synthesize them increases in mice lacking UT-B. AQP2 and AQP3 facilitate water transfer in the kidney collecting duct’s principal cells. The increase in AQP2 and AQP3 would partially compensate for the lack of UT-B and prevent an even greater reduction in urine concentrating ability than would occur if they were not increased.
The scientists speculate that the increase in UT-A2 may be an adaptation that attempts to decrease the loss of urea from the kidney medulla. That is, the loss of one urea recycling pathway, UT-B, induces an adaptive response that increases the function of the other urea recycling pathway.