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| Main Authors: | , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
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International immunopharmacology
2026
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/41270641/ |
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| _version_ | 1868266125080395778 |
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| author | Wang, Guifa Zhou, Yifan Liu, Yuhan Zhang, Nan Qiu, Xia Zhou, Zijian Pu, Yexin Liang, Hui Xue, Meilan |
| author_facet | Wang, Guifa Zhou, Yifan Liu, Yuhan Zhang, Nan Qiu, Xia Zhou, Zijian Pu, Yexin Liang, Hui Xue, Meilan Wang, Guifa Zhou, Yifan Liu, Yuhan Zhang, Nan Qiu, Xia Zhou, Zijian Pu, Yexin Liang, Hui Xue, Meilan |
| collection | PubMed - marine biology |
| contents | Fucoidan oligosaccharides alleviated alcoholic liver fibrosis by blocking the core fucosylation of TGF-β receptors via the JAK/STAT3/FUT8 axis. Wang, Guifa Zhou, Yifan Liu, Yuhan Zhang, Nan Qiu, Xia Zhou, Zijian Pu, Yexin Liang, Hui Xue, Meilan Animals STAT3 Transcription Factor Polysaccharides Mice Male Liver Cirrhosis, Alcoholic Oligosaccharides Mice, Inbred C57BL Signal Transduction Hepatic Stellate Cells Janus Kinases Humans Liver Alcoholic liver fibrosis (ALF) is a severe hepatic disorder caused by chronic excessive alcohol consumption, involving hepatic stellate cells (HSCs) activation. Fucoidan oligosaccharides (FOS) are marine algae-derived oligosaccharides with diverse biological activities. This study investigated FOS's protective effects against ALF and its molecular mechanisms through in vivo and in vitro experiments. The results indicated that FOS ameliorated liver function injury in mice. FOS reduced serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) while increasing the levels of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). FOS alleviated hepatic steatosis and inflammation, and reduced hepatic lipid accumulation and blood lipid levels. Moreover, FOS inhibited the activation of hepatic stellate cells (HSCs), downregulated the expression of α-smooth muscle actin (α-SMA), Collagen - I, and Collagen - III. Bioinformatic analysis integrating five databases with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that Signal Transducer and Activator of Transcription-3 (STAT3) is the upstream regulatory gene of fucosyltransferase 8 (FUT8) and closely associates with the Janus Kinase (JAK)/STAT signaling pathway. Molecular docking results indicated that FOS could bind to JAK1 (binding energy = -5.4 kcal/mol). Further experimental studies demonstrated that FOS downregulated the expression of FUT8 and the core fucosylation of TGF-β type I receptor (ALK5) by inhibiting the JAK/STAT3 signaling pathway, thereby suppressing the activity of the TGF-β/Smad signaling pathway. These results demonstrate that FOS, as a natural marine algae-derived functional oligosaccharide, exhibits potential to ameliorate ALF through suppression of the JAK/STAT3/FUT8 axis. |
| format | Artículo científico |
| id | pubmed_41270641 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | International immunopharmacology |
| record_format | pubmed |
| spellingShingle | Fucoidan oligosaccharides alleviated alcoholic liver fibrosis by blocking the core fucosylation of TGF-β receptors via the JAK/STAT3/FUT8 axis. Wang, Guifa Zhou, Yifan Liu, Yuhan Zhang, Nan Qiu, Xia Zhou, Zijian Pu, Yexin Liang, Hui Xue, Meilan Animals STAT3 Transcription Factor Polysaccharides Mice Male Liver Cirrhosis, Alcoholic Oligosaccharides Mice, Inbred C57BL Signal Transduction Hepatic Stellate Cells Janus Kinases Humans Liver Fucoidan oligosaccharides alleviated alcoholic liver fibrosis by blocking the core fucosylation of TGF-β receptors via the JAK/STAT3/FUT8 axis. Wang, Guifa Zhou, Yifan Liu, Yuhan Zhang, Nan Qiu, Xia Zhou, Zijian Pu, Yexin Liang, Hui Xue, Meilan Animals STAT3 Transcription Factor Polysaccharides Mice Male Liver Cirrhosis, Alcoholic Oligosaccharides Mice, Inbred C57BL Signal Transduction Hepatic Stellate Cells Janus Kinases Humans Liver Alcoholic liver fibrosis (ALF) is a severe hepatic disorder caused by chronic excessive alcohol consumption, involving hepatic stellate cells (HSCs) activation. Fucoidan oligosaccharides (FOS) are marine algae-derived oligosaccharides with diverse biological activities. This study investigated FOS's protective effects against ALF and its molecular mechanisms through in vivo and in vitro experiments. The results indicated that FOS ameliorated liver function injury in mice. FOS reduced serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) while increasing the levels of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). FOS alleviated hepatic steatosis and inflammation, and reduced hepatic lipid accumulation and blood lipid levels. Moreover, FOS inhibited the activation of hepatic stellate cells (HSCs), downregulated the expression of α-smooth muscle actin (α-SMA), Collagen - I, and Collagen - III. Bioinformatic analysis integrating five databases with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that Signal Transducer and Activator of Transcription-3 (STAT3) is the upstream regulatory gene of fucosyltransferase 8 (FUT8) and closely associates with the Janus Kinase (JAK)/STAT signaling pathway. Molecular docking results indicated that FOS could bind to JAK1 (binding energy = -5.4 kcal/mol). Further experimental studies demonstrated that FOS downregulated the expression of FUT8 and the core fucosylation of TGF-β type I receptor (ALK5) by inhibiting the JAK/STAT3 signaling pathway, thereby suppressing the activity of the TGF-β/Smad signaling pathway. These results demonstrate that FOS, as a natural marine algae-derived functional oligosaccharide, exhibits potential to ameliorate ALF through suppression of the JAK/STAT3/FUT8 axis. |
| title | Fucoidan oligosaccharides alleviated alcoholic liver fibrosis by blocking the core fucosylation of TGF-β receptors via the JAK/STAT3/FUT8 axis. |
| topic | Animals STAT3 Transcription Factor Polysaccharides Mice Male Liver Cirrhosis, Alcoholic Oligosaccharides Mice, Inbred C57BL Signal Transduction Hepatic Stellate Cells Janus Kinases Humans Liver |
| url | https://pubmed.ncbi.nlm.nih.gov/41270641/ |