title: Increased expression of SLC2A9 decreases urate excretion from the kidney.
abstract: Urate is the final metabolite of purine in humans. Renal urate handling is clinically important because under-reabsorption or underexcretion causes hypouricemia or hyperuricemia, respectively. We have identified a urate-anion exchanger, URAT1, localized at the apical side and a voltage-driven urate efflux transporter, URATv1, expressed at the basolateral side of the renal proximal tubules. URAT1 and URATv1 are vital to renal urate reabsorption because the experimental data have illustrated that functional loss of these transporter proteins affords hypouricemia. While mutations affording enhanced function via these transporter proteins on urate handling is unknown, we have constructed kidney-specific transgenic (Tg) mice for URAT1 or URATv1 to investigate this problem. In our study, each transgene was under the control of the mouse URAT1 promoter so that transgene expression was directed to the kidney. Plasma urate concentrations in URAT1 and URATv1 Tg mice were not significantly different from that in wild-type (WT) mice. Urate excretion in URAT1 Tg mice was similar to that in WT mice, while URATv1 Tg mice excreted more urate compared with WT. Our results suggest that hyperfunctioning URATv1 in the kidney can lead to increased urate reabsorption and may contribute to the development of hyperuricemia.
authors: Department of Pharmacology and Toxicology, School of Medicine, Kyorin University, Tokyo, Japan. kimura@ks.kyorin-u.ac.jp
authors: Toru
authors: T
authors: Kimura
authors: Sirirat
authors: S
authors: Amonpatumrat
authors: Ai
authors: A
authors: Tsukada
authors: Toshiyuki
authors: T
authors: Fukutomi
authors: Promsuk
authors: P
authors: Jutabha
authors: Thanapol
authors: T
authors: Thammapratip
authors: Eun J
authors: EJ
authors: Lee
authors: Kimiyoshi
authors: K
authors: Ichida
authors: Naohiko
authors: N
authors: Anzai
authors: Hiroyuki
authors: H
authors: Sakurai
mesh_terms: D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014527:Uric Acid / Q000097:blood / Q000378:metabolism* / Q000652:urine
chemical_list: D051246:Glucose Transport Proteins, Facilitative; C411811:SLC2A9 protein, human; D014527:Uric Acid