Alcohol dehydrogenase III exacerbates liver fibrosis by enhancing stellate cell activation and suppressing natural killer cells in mice
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Yi H.-S. | - |
dc.contributor.author | Lee Y.-S. | - |
dc.contributor.author | Byun J.-S. | - |
dc.contributor.author | Seo W. | - |
dc.contributor.author | Jeong J.-M. | - |
dc.contributor.author | Park O. | - |
dc.contributor.author | Duester G. | - |
dc.contributor.author | Haseba T. | - |
dc.contributor.author | Kim S.C. | - |
dc.contributor.author | Park K.-G. | - |
dc.contributor.author | Gao B. | - |
dc.contributor.author | Jeong W.-I. | - |
dc.date.available | 2020-11-02T19:44:01Z | - |
dc.date.issued | 2014 | - |
dc.identifier.issn | 0270-9139 | - |
dc.identifier.issn | 1527-3350 | - |
dc.identifier.uri | https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/9972 | - |
dc.description.abstract | The important roles of retinols and their metabolites have recently been emphasized in the interactions between hepatic stellate cells (HSCs) and natural killer (NK) cells. Nevertheless, the expression and role of retinol metabolizing enzyme in both cell types have yet to be clarified. Thus, we investigated the expression of retinol metabolizing enzyme and its role in liver fibrosis. Among several retinol metabolizing enzymes, only alcohol dehydrogenase (ADH) 3 expression was detected in isolated HSCs and NK cells, whereas hepatocytes express all of them. In vitro treatment with 4-methylpyrazole (4-MP), a broad ADH inhibitor, or depletion of the ADH3 gene down-regulated collagen and transforming growth factor-β1 (TGF-β1) gene expression, but did not affect α-smooth muscle actin gene expression in cultured HSCs. Additionally, in vitro, treatments with retinol suppressed NK cell activities, whereas inhibition of ADH3 enhanced interferon-γ (IFN-γ) production and cytotoxicity of NK cells against HSCs. In vivo, genetic depletion of the ADH3 gene ameliorated bile duct ligation- and carbon tetrachloride-induced liver fibrosis, in which a higher number of apoptotic HSCs and an enhanced activation of NK cells were detected. Freshly isolated HSCs from ADH3-deficient mice showed reduced expression of collagen and TGF-β1, but enhanced expression of IFN-γ was detected in NK cells from these mice compared with those of control mice. Using reciprocal bone marrow transplantation of wild-type and ADH3-deficient mice, we demonstrated that ADH3 deficiency in both HSCs and NK cells contributed to the suppressed liver fibrosis. Conclusion: ADH3 plays important roles in promoting liver fibrosis by enhancing HSC activation and inhibiting NK cell activity, and could be used as a potential therapeutic target for the treatment of liver fibrosis. © 2014 by the American Association for the Study of Liver Diseases. | - |
dc.format.extent | 10 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | John Wiley and Sons Inc. | - |
dc.title | Alcohol dehydrogenase III exacerbates liver fibrosis by enhancing stellate cell activation and suppressing natural killer cells in mice | - |
dc.type | Article | - |
dc.publisher.location | 미국 | - |
dc.identifier.doi | 10.1002/hep.27137 | - |
dc.identifier.scopusid | 2-s2.0-84906498641 | - |
dc.identifier.bibliographicCitation | Hepatology, v.60, no.3, pp 1044 - 1053 | - |
dc.citation.title | Hepatology | - |
dc.citation.volume | 60 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 1044 | - |
dc.citation.endPage | 1053 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordPlus | 4 methylpyrazole | - |
dc.subject.keywordPlus | alcohol dehydrogenase | - |
dc.subject.keywordPlus | alcohol dehydrogenase III | - |
dc.subject.keywordPlus | alpha smooth muscle actin | - |
dc.subject.keywordPlus | gamma interferon | - |
dc.subject.keywordPlus | interleukin 6 | - |
dc.subject.keywordPlus | monocyte chemotactic protein 1 | - |
dc.subject.keywordPlus | retinol | - |
dc.subject.keywordPlus | transforming growth factor beta1 | - |
dc.subject.keywordPlus | unclassified drug | - |
dc.subject.keywordPlus | animal cell | - |
dc.subject.keywordPlus | animal experiment | - |
dc.subject.keywordPlus | animal model | - |
dc.subject.keywordPlus | apoptosis | - |
dc.subject.keywordPlus | article | - |
dc.subject.keywordPlus | bile duct ligation | - |
dc.subject.keywordPlus | bone marrow transplantation | - |
dc.subject.keywordPlus | carbon tetrachloride-induced liver fibrosis | - |
dc.subject.keywordPlus | cell activation | - |
dc.subject.keywordPlus | cell proliferation | - |
dc.subject.keywordPlus | controlled study | - |
dc.subject.keywordPlus | disease exacerbation | - |
dc.subject.keywordPlus | down regulation | - |
dc.subject.keywordPlus | enzyme inhibition | - |
dc.subject.keywordPlus | enzyme metabolism | - |
dc.subject.keywordPlus | gene expression | - |
dc.subject.keywordPlus | human | - |
dc.subject.keywordPlus | human cell | - |
dc.subject.keywordPlus | in vitro study | - |
dc.subject.keywordPlus | in vivo study | - |
dc.subject.keywordPlus | male | - |
dc.subject.keywordPlus | mouse | - |
dc.subject.keywordPlus | natural killer cell | - |
dc.subject.keywordPlus | nonhuman | - |
dc.subject.keywordPlus | pancreatic stellate cell | - |
dc.subject.keywordPlus | priority journal | - |
dc.subject.keywordPlus | protein depletion | - |
dc.subject.keywordPlus | real time polymerase chain reaction | - |
dc.subject.keywordPlus | reverse transcription polymerase chain reaction | - |
dc.subject.keywordPlus | Aldehyde Oxidoreductases | - |
dc.subject.keywordPlus | Animals | - |
dc.subject.keywordPlus | Bone Marrow Transplantation | - |
dc.subject.keywordPlus | Hepatic Stellate Cells | - |
dc.subject.keywordPlus | Interferon-gamma | - |
dc.subject.keywordPlus | Killer Cells, Natural | - |
dc.subject.keywordPlus | Liver Cirrhosis | - |
dc.subject.keywordPlus | Male | - |
dc.subject.keywordPlus | Mice | - |
dc.subject.keywordPlus | Mice, Inbred C57BL | - |
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