Kidney Week

Abstract: TH-PO483

Regulation of ABCG2 Transporter and Uric Acid Metabolism in a Model of Hyperuricemia

Session Information

• Fluid and Electrolytes: Basic - I
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid and Electrolytes

• 901 Fluid and Electrolytes: Basic

Authors

• Morimoto, Chikayuki, Teikyo University School of Medicine, Tokyo, TOKYO, Japan

Chikayuki Morimoto,

• Tamura, Yoshifuru, Teikyo University School of Medicine , Tokyo, Japan

Yoshifuru Tamura,

• Kuribayashi-Okuma, Emiko, Teikyo University School of Medicine , Tokyo, Japan

Emiko Kuribayashi-Okuma,

• Murase, Takayo, Sanwa Kagaku Kenkyusyo Co., Ltd., Inabe-shi, Japan

Takayo Murase,

• Nakamura, Takashi, Sanwa Kagaku Kenkyusho, Inabe, Japan

Takashi Nakamura,

• Nemoto, Yoshikazu, Teikyo University School of Medicine, Tokyo, TOKYO, Japan

Yoshikazu Nemoto,

• Asakawa, Shinichiro, Teikyo University School of Medicine, Tokyo, TOKYO, Japan

Shinichiro Asakawa,

• Fujigaki, Yoshihide, Teikyo University School of Medicine, Department of Internal Medicine, Tokyo, Japan

Yoshihide Fujigaki,

• Uchida, Shunya, Teikyo University School of Medicine, Tokyo, TOKYO, Japan

Shunya Uchida,

• Shibata, Shigeru, Teikyo University School of Medicine, Tokyo, TOKYO, Japan

Shigeru Shibata,

Background

Hyperuricemia is one of the most frequent complications in chronic kidney disease (CKD). Previously, we showed that the gene expression of the urate transporter ATP-binding cassette subfamily G member 2 (ABCG2) is upregulated in the ileum in the rat remnant kidney model (Yano et al. Clin Exp Nephrol 2014), indicating that the intestine may participate in uric acid metabolism in CKD. However, the role of each part of the intestinal tract in uric acid metabolism in normal and hyperuricemic states have not been clarified. In this study, uric acid concentrations and ABCG2 expression in the different part of intestine were evaluated in normal and hyperuricemia model rats.

Methods

Using Sprague-Dawley rats, we evaluated ABCG2 expression in each part of the intestinal tract by immunofluorescent study. Uric acid concentrations in the serum and in the tissue homogenates were measured by LC/MS. We also evaluated the ABCG2 levels in the intestine of hyperuricemia rats. Hyperuricemia was induced by feeding a diet containing 5% oxonic acid, the uricase inhibitor.

Results

In the intestinal tract of normal rats, the concentration of tissue uric acid (in μg/g tissue) was 5-10 times higher in duodenum and jejunum than in ileum and transverse colon (duodenum 102 ± 16; jejunum 112 ± 16; ileum 17 ± 8.2; transverse colon 7 ± 4). Co-staining of ABCG2 and villin revealed that ABCG2 was highly present in the villus and crypt of the duodenum. Administration of oxonic acid increased serum uric acid levels by 2.1 fold (P < 0.05). Comparison of the ABCG2 staining between control and hyperuricemic rats indicated that ABCG2 was upregulated in the ileum by hyperuricemia.

Conclusion

ABCG2 is highly expressed in the duodenum and jejunum at basal condition. However, Hyperuricemia upregulates ABCG2 in the ileum. These data are consistent with our previous studies showing the upregulation of ABCG2 in the ileum in the rat remnant kidney model, and suggest a compensatory role of ileum in hyperuricemic states.