Clinical and experimental nephrology · 2013
Uric acid transporter ABCG2 is increased in the intestine of the 5/6 nephrectomy rat model of chronic kidney disease.
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Yano Hirofumi, Tamura Yoshifuru, Kobayashi Kana, Tanemoto Masayuki, Uchida Shunya
Аннотация
BACKGROUND: Uric acid (UA) remains a risk factor of chronic kidney disease (CKD). Therefore, it is important to clarify the mechanism of UA excretion in CKD. The specific mechanisms of extrarenal excretion from the intestine are unknown. We evaluated the expression of the UA transporter in the intestinal tract--the ATP-binding cassette transporter G2 (ABCG2)--in a 5/6 nephrectomy rat model of CKD.
METHODS: Male Wistar rats (6 weeks old) were randomly assigned to the 5/6 nephrectomized (Nx) group or the sham-operated control group. Urine and blood samples were collected every 4 weeks. All the rats were killed at 8 weeks to obtain liver, duodenum, jejunum, ileum, and transverse colon tissues. Uricase activity was measured in the liver. Expression of ABCG2 in intestinal mucosa was measured with real time polymerase chain reaction (PCR).
RESULTS: The Nx group showed significantly decreased urine UA excretion/body weight and UA clearance compared to the control group at 4 and 8 weeks after nephrectomy. In contrast, serum UA and uricase activity were not significant. The expression of ABCG2 in the ileum of the Nx group showed significantly increased upregulation, while no changes were seen in the intestines of the control group.
CONCLUSIONS: The Nx rats exhibited lower excretion of urine UA and over-expression of ABCG2 in the ileum. The fact that serum UA did not increase despite the decrease in UA excretion suggests that an excretory pathway other than the kidney, probably the intestine, may operate in a complementary role that corroborates the increase in ABCG2 expression in the ileum.
METHODS: Male Wistar rats (6 weeks old) were randomly assigned to the 5/6 nephrectomized (Nx) group or the sham-operated control group. Urine and blood samples were collected every 4 weeks. All the rats were killed at 8 weeks to obtain liver, duodenum, jejunum, ileum, and transverse colon tissues. Uricase activity was measured in the liver. Expression of ABCG2 in intestinal mucosa was measured with real time polymerase chain reaction (PCR).
RESULTS: The Nx group showed significantly decreased urine UA excretion/body weight and UA clearance compared to the control group at 4 and 8 weeks after nephrectomy. In contrast, serum UA and uricase activity were not significant. The expression of ABCG2 in the ileum of the Nx group showed significantly increased upregulation, while no changes were seen in the intestines of the control group.
CONCLUSIONS: The Nx rats exhibited lower excretion of urine UA and over-expression of ABCG2 in the ileum. The fact that serum UA did not increase despite the decrease in UA excretion suggests that an excretory pathway other than the kidney, probably the intestine, may operate in a complementary role that corroborates the increase in ABCG2 expression in the ileum.
Предметные рубрики MeSH
ATP Binding Cassette Transporter, Subfamily G, Member 2ATP-Binding Cassette TransportersAnimalsDisease Models, AnimalIleumIntestinal EliminationLiverMaleNephrectomyRNA, MessengerRatsRats, WistarReal-Time Polymerase Chain ReactionRenal EliminationRenal Insufficiency, ChronicTime FactorsUp-RegulationUrate OxidaseUric Acid