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Open AccessArticle

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

1
Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan 35053, Taiwan
2
Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University/Chang Gung Memorial Hospital at Linkou, Taoyuan 33302, Taiwan
3
Research and Development Center, Hi-Q Marine Biotech International Ltd. Songshan District, Taipei 10561, Taiwan
4
Institute of Bioinformatics and Structural Biology, National Tsing-Hua University, Hsinchu 30013, Taiwan
5
Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30010, Taiwan
6
Program in Environmental and Occupational Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this paper.
Biomolecules 2020, 10(6), 898; https://doi.org/10.3390/biom10060898
Received: 6 April 2020 / Revised: 9 June 2020 / Accepted: 10 June 2020 / Published: 12 June 2020
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. View Full-Text
Keywords: oligo-fucoidan; hepatocyte nuclear factor 4 alpha (HNF4A); hepatocyte oligo-fucoidan; hepatocyte nuclear factor 4 alpha (HNF4A); hepatocyte
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Cheng, C.-C.; Yang, W.-Y.; Hsiao, M.-C.; Lin, K.-H.; Lee, H.-W.; Yuh, C.-H. Transcriptomically Revealed Oligo-Fucoidan Enhances the Immune System and Protects Hepatocytes via the ASGPR/STAT3/HNF4A Axis. Biomolecules 2020, 10, 898.

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