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Fucoidan from Laminaria japonica Inhibits Expression of GLUT9 and URAT1 via PI3K/Akt,JNK and NF-κB Pathways in Uric Acid-Exposed HK-2 Cells
Authors:Yu Zhang  Xiaohui Tan  Zhen Lin  Fangping Li  Chunyan Yang  Haiying Zheng  Lingyu Li  Huazhong Liu  Jianghua Shang
Institution:1.College of Chemistry and Environmental Science, Guangdong Ocean University, Zhanjiang 524088, China; (Y.Z.); (X.T.); (Z.L.); (F.L.);2.Guangxi Key Laboratory of Buffalo Genetics, Reproduction and Breeding, Guangxi Buffalo Research Institute, Chinese Academy of Agricultural Sciences, Nanning 530001, China; (C.Y.); (H.Z.); (L.L.)
Abstract:This work aimed to investigate the effect of fucoidan (FPS) on urate transporters induced by uric acid (UA). The results showed that UA stimulated the expression of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) in HK-2 cells, and FPS could reverse the effect. Moreover, UA could activate NF-κB, JNK and PI3K/Akt pathways, but both pathway inhibitors and FPS inhibited the UA-induced activation of these three pathways. These data suggested that FPS effectively inhibited the expression induction of reabsorption transporters URAT1 and GLUT9 by UA, through repressing the activation of NF-κB, JNK and PI3K/Akt signal pathways in HK-2 cells. The in vitro research findings support the in vivo results that FPS reduces serum uric acid content in hyperuricemia mice and rats through inhibiting the expression of URAT1 and GLUT9 in renal tubular epithelial cells. This study provides a theoretical basis for the application of FPS in the treatment of hyperuricemia.
Keywords:fucoidan  uric acid  urate transporter 1  glucose transporter 9
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