https://scholars.lib.ntu.edu.tw/handle/123456789/416883
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Kuo Y.-C. | en_US |
dc.contributor.author | Chen I.-Y. | en_US |
dc.contributor.author | SHIN CHANG | en_US |
dc.contributor.author | Wu S.-C. | en_US |
dc.contributor.author | Hung T.-M. | en_US |
dc.contributor.author | PO-HUANG LEE | en_US |
dc.contributor.author | Shimotohno K. | en_US |
dc.contributor.author | MING-FU CHANG | en_US |
dc.creator | Kuo Y.-C.;Chen I.-Y.;Chang, S.C.;Wu S.-C.;Hung T.-M.;Lee P.-H.;Shimotohno K.;Ming-Fu Chang | - |
dc.date.accessioned | 2019-08-30T02:32:30Z | - |
dc.date.available | 2019-08-30T02:32:30Z | - |
dc.date.issued | 2014 | - |
dc.identifier.issn | 1478-3223 | - |
dc.identifier.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84908229164&doi=10.1111%2fliv.12389&partnerID=40&md5=14bbe4cd5fb339c1b068b77003055f8a | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/416883 | - |
dc.description.abstract | Background & Aims: Hepatitis C virus (HCV) infection is highly associated with the type 2 diabetes mellitus, but the detailed mechanisms by which the viral proteins are involved in the clinical outcome remain unclear. Methods: A cDNA microarray analysis was performed following introducing an NS5A-encoding plasmid or a control vector into a mouse system by hydrodynamics-based transfection. Differentially expressed genes that are associated with gluconeogenesis were selected and their expression levels in HCV patients, in NS5A-expressing systems, and in the viral subgenomic replicon system were further examined by real-time quantitative polymerase chain reaction and Western blot analysis. Results: Differential gene expression including an upregulation of the gluconeogenic rate-limiting enzyme phosphoenolpyruvate carboxykinase (PEPCK) compared with controls was detected in mouse hepatocytes expressing HCV NS5A and in HCV patients with diabetes. In addition, an NS5A-dependent increase in glucose production was demonstrated in human primary hepatocytes. The upregulation of PEPCK and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) were also detected in NS5A-expressing cells and in the viral genotype 1b subgenomic replicon system. Further studies demonstrated that the NS5A-mediated upregulation of PEPCK and PGC-1α genes were resulted from the activation of PI3K-Akt and JNK signalling pathways. In addition, the expression levels of the forkhead transcription factor FoxO1 and the liver-enriched transcription factor HNF-4α were increased in HCV NS5A-expressing cells. Conclusions: By upregulating the expression of PEPCK gene via its transactivators FoxO1 and HNF-4α, and the coactivator PGC-1α, the NS5A promotes the production of hepatic glucose which may contribute to the development of HCV-associated type 2 diabetes mellitus. ? 2013 John Wiley & Sons A/S. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Blackwell Publishing Ltd | en_US |
dc.relation.ispartof | Liver International | en_US |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | hepatocyte nuclear factor 4alpha; nonstructural protein 5A; peroxisome proliferator activated receptor gamma coactivator 1alpha; phosphoenolpyruvate carboxylase; protein kinase B; stress activated protein kinase; transcription factor FKHR; glucose; mitogen activated protein kinase kinase 4; NS-5 protein, hepatitis C virus; oncoprotein; phosphoenolpyruvate carboxykinase (ATP); virus protein; animal cell; Article; controlled study; enzyme activation; enzyme regulation; gene expression; gluconeogenesis; Hepatitis C virus; human; human cell; mouse; non insulin dependent diabetes mellitus; nonhuman; polymerase chain reaction; signal transduction; upregulation; Western blotting; animal; complication; Diabetes Mellitus, Type 2; DNA microarray; gene expression regulation; genetic transfection; gluconeogenesis; Hepacivirus; hepatitis C; liver cell; metabolism; physiology; real time polymerase chain reaction; virology; Animals; Blotting, Western; Diabetes Mellitus, Type 2; Gene Expression Regulation; Gluconeogenesis; Glucose; Hepacivirus; Hepatitis C; Hepatocytes; Humans; MAP Kinase Kinase 4; Mice; Oligonucleotide Array Sequence Analysis; Oncogene Protein v-akt; Phosphoenolpyruvate Carboxykinase (ATP); Real-Time Polymerase Chain Reaction; Signal Transduction; Transfection; Viral Nonstructural Proteins | - |
dc.title | Hepatitis C virus NS5A protein enhances gluconeogenesis through upregulation of Akt-/JNK-PEPCK signalling pathways | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1111/liv.12389 | - |
dc.identifier.pmid | 25360475 | - |
dc.identifier.scopus | 2-s2.0-84908229164 | - |
dc.relation.pages | 1358-1368 | en_US |
dc.relation.journalvolume | 34 | en_US |
dc.relation.journalissue | 9 | en_US |
item.openairetype | journal article | - |
item.fulltext | no fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.grantfulltext | none | - |
item.languageiso639-1 | en_US | - |
item.cerifentitytype | Publications | - |
crisitem.author.dept | Microbiology | - |
crisitem.author.dept | Surgery | - |
crisitem.author.dept | Surgery-NTUH | - |
crisitem.author.dept | Biochemistry and Molecular Biology | - |
crisitem.author.orcid | 0000-0002-0365-8364 | - |
crisitem.author.orcid | 0000-0001-5831-035X | - |
crisitem.author.orcid | 0000-0001-7062-3578 | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
顯示於: | 微生物學科所 |
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