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
-
- 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
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):.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping