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ZFIN ID: ZDB-PUB-200618-1
Transcriptomically Revealed Oligo-Fucoidan Enhances the Immune System and Protects Hepatocytes via the ASGPR/STAT3/HNF4A Axis
Cheng, C.C., Yang, W.Y., Hsiao, M.C., Lin, K.H., Lee, H.W., Yuh, C.H.
Date: 2020
Source: Biomolecules   10(6): (Journal)
Registered Authors: Yang, Wan-Yu, Yuh, Chiou-Hwa (Cathy)
Keywords: hepatocyte, hepatocyte nuclear factor 4 alpha (HNF4A), oligo-fucoidan
Microarrays: GEO:GSE148324
MeSH Terms:
  • Animals
  • Asialoglycoprotein Receptor/metabolism
  • Cell Survival/drug effects
  • Cell Survival/genetics
  • Cells, Cultured
  • Cytoprotection/drug effects*
  • Cytoprotection/genetics
  • Dietary Supplements
  • Gene Expression Profiling
  • Hepatocyte Nuclear Factor 4/metabolism
  • Hepatocytes/drug effects*
  • Hepatocytes/metabolism
  • Hepatocytes/physiology
  • Immune System/drug effects*
  • Immune System/metabolism
  • Mice
  • Mice, Inbred BALB C
  • Microarray Analysis
  • Polysaccharides/chemistry
  • Polysaccharides/pharmacology*
  • STAT3 Transcription Factor/metabolism
  • Signal Transduction/drug effects
  • Signal Transduction/genetics
  • Transcriptome/drug effects*
  • Zebrafish
PubMed: 32545625 Full text @ Biomolecules
Oligo-fucoidan, a sulfated polysaccharide extracted from brown seaweed, exhibits anti-inflammatory and anti-tumor effects. However, the knowledge concerning the detailed mechanism of oligo-fucoidan on liver cells is obscure. In this study, we investigate the effect of oligo-fucoidan in normal hepatocytes by transcriptomic analysis. Using an oligo-fucoidan oral gavage in wild-type adult zebrafish, we find that oligo-fucoidan pretreatment enhances the immune system and anti-viral genes in hepatocytes. Oligo-fucoidan pretreatment also decreases the expression of lipogenic enzymes and liver fibrosis genes. Using pathway analysis, we identify hepatocyte nuclear factor 4 alpha (HNF4A) to be the potential driver gene. We further investigate whether hepatocyte nuclear factor 4 alpha (HNF4A) could be induced by oligo-fucoidan and the underlying mechanism. Therefore, a normal hepatocyte clone 9 cell as an in vitro model was used. We demonstrate that oligo-fucoidan increases cell viability, Cyp3a4 activity, and Hnf4a expression in clone 9 cells. We further demonstrate that oligo-fucoidan might bind to asialoglycoprotein receptors (ASGPR) in normal hepatocytes through both in vitro and in vivo competition assays. This binding, consequently activating the signal transducer and activator of transcription 3 (STAT3), increases the expression of the P1 isoform of HNF4A. According to our data, we suggest that oligo-fucoidan not only enhances the gene expression associated with anti-viral ability and immunity, but also increases P1-HNF4A levels through ASGPR/STAT3 axis, resulting in protecting hepatocytes.