PUBLICATION

Transcriptomically Revealed Oligo-Fucoidan Enhances the Immune System and Protects Hepatocytes via the ASGPR/STAT3/HNF4A Axis

Authors
Cheng, C.C., Yang, W.Y., Hsiao, M.C., Lin, K.H., Lee, H.W., Yuh, C.H.
ID
ZDB-PUB-200618-1
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
Datasets
GEO:GSE148324
MeSH Terms
  • Polysaccharides/chemistry
  • Polysaccharides/pharmacology*
  • Zebrafish
  • Cell Survival/drug effects
  • Cell Survival/genetics
  • Transcriptome/drug effects*
  • Mice
  • Microarray Analysis
  • Cells, Cultured
  • Hepatocyte Nuclear Factor 4/metabolism
  • Immune System/drug effects*
  • Immune System/metabolism
  • Mice, Inbred BALB C
  • Signal Transduction/drug effects
  • Signal Transduction/genetics
  • Gene Expression Profiling
  • Asialoglycoprotein Receptor/metabolism
  • Cytoprotection/drug effects*
  • Cytoprotection/genetics
  • Animals
  • Dietary Supplements
  • Hepatocytes/drug effects*
  • Hepatocytes/metabolism
  • Hepatocytes/physiology
  • STAT3 Transcription Factor/metabolism
(all 25)
PubMed
32545625 Full text @ Biomolecules
Abstract
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.
Genes / Markers
Figures
No images available
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Your Input Welcome
We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly.
Citation
Cheng, C.C., Yang, W.Y., Hsiao, M.C., Lin, K.H., Lee, H.W., Yuh, C.H. (2020) Transcriptomically Revealed Oligo-Fucoidan Enhances the Immune System and Protects Hepatocytes via the ASGPR/STAT3/HNF4A Axis. Biomolecules. 10(6):.