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

Mar Drugs. 2021 Apr 23;19(5):238. doi: 10.3390/md19050238.

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; glucose transporter 9; urate transporter 1; uric acid.

MeSH terms

  • Cell Line
  • Glucose Transport Proteins, Facilitative / metabolism*
  • Gout Suppressants / isolation & purification
  • Gout Suppressants / pharmacology*
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Kidney Tubules, Proximal / drug effects*
  • Kidney Tubules, Proximal / enzymology
  • Laminaria* / chemistry
  • NF-kappa B / metabolism*
  • Organic Anion Transporters / metabolism*
  • Organic Cation Transport Proteins / metabolism*
  • Phosphatidylinositol 3-Kinase / metabolism*
  • Polysaccharides / isolation & purification
  • Polysaccharides / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction
  • Uric Acid / toxicity

Substances

  • Glucose Transport Proteins, Facilitative
  • Gout Suppressants
  • NF-kappa B
  • Organic Anion Transporters
  • Organic Cation Transport Proteins
  • Polysaccharides
  • SLC22A12 protein, human
  • SLC2A9 protein, human
  • Uric Acid
  • fucoidan
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • JNK Mitogen-Activated Protein Kinases