Cited 508 times in
NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis
DC Field | Value | Language |
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dc.contributor.author | 백용한 | - |
dc.date.accessioned | 2015-07-15T16:46:19Z | - |
dc.date.available | 2015-07-15T16:46:19Z | - |
dc.date.issued | 2003 | - |
dc.identifier.issn | 0021-9738 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/113568 | - |
dc.description.abstract | Angiotensin II (Ang II) is a pro-oxidant and fibrogenic cytokine. We investigated the role of NADPH oxidase in Ang II–induced effects in hepatic stellate cells (HSCs), a fibrogenic cell type. Human HSCs express mRNAs of key components of nonphagocytic NADPH oxidase. Ang II phosphorylated p47phox, a regulatory subunit of NADPH oxidase, and induced reactive oxygen species formation via NADPH oxidase activity. Ang II phosphorylated AKT and MAPKs and increased AP-1 DNA binding in a redox-sensitive manner. Ang II stimulated DNA synthesis, cell migration, procollagen α1(I) mRNA expression, and secretion of TGF-β1 and inflammatory cytokines. These effects were attenuated by N-acetylcysteine and diphenylene iodonium, an NADPH oxidase inhibitor. Moreover, Ang II induced upregulation of genes potentially involved in hepatic wound-healing response in a redox-sensitive manner, as assessed by microarray analysis. HSCs isolated from p47phox–/– mice displayed a blunted response to Ang II compared with WT cells. We also assessed the role of NADPH oxidase in experimental liver fibrosis. After bile duct ligation, p47phox–/– mice showed attenuated liver injury and fibrosis compared with WT counterparts. Moreover, expression of smooth muscle α-actin and expression of TGF-β1 were reduced in p47phox–/– mice. Thus, NADPH oxidase mediates the actions of Ang II on HSCs and plays a critical role in liver fibrogenesis. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 1383~1394 | - |
dc.relation.isPartOf | JOURNAL OF CLINICAL INVESTIGATION | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Angiotensin II/pharmacology* | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Cells, Cultured | - |
dc.subject.MESH | DNA/metabolism | - |
dc.subject.MESH | Enzyme Activation | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Lipid Peroxidation/drug effects | - |
dc.subject.MESH | Liver/cytology* | - |
dc.subject.MESH | Liver/drug effects | - |
dc.subject.MESH | Liver/metabolism | - |
dc.subject.MESH | Liver Cirrhosis, Experimental/etiology* | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Inbred C57BL | - |
dc.subject.MESH | Mitogen-Activated Protein Kinases/physiology | - |
dc.subject.MESH | NADPH Oxidases/physiology* | - |
dc.subject.MESH | Phosphoproteins/physiology | - |
dc.subject.MESH | Reactive Oxygen Species | - |
dc.subject.MESH | Signal Transduction/physiology* | - |
dc.subject.MESH | Transcription Factor AP-1/metabolism | - |
dc.title | NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학) | - |
dc.contributor.googleauthor | Ramón Bataller | - |
dc.contributor.googleauthor | Robert F. Schwabe | - |
dc.contributor.googleauthor | David A. Brenner | - |
dc.contributor.googleauthor | John J. Lemasters | - |
dc.contributor.googleauthor | Curt H. Hagedorn | - |
dc.contributor.googleauthor | Robert Schoonhoven | - |
dc.contributor.googleauthor | Ting Qian | - |
dc.contributor.googleauthor | Jeffrey Lindquist | - |
dc.contributor.googleauthor | Yong Han Paik | - |
dc.contributor.googleauthor | Liu Yang | - |
dc.contributor.googleauthor | Youkyung H. Choi | - |
dc.identifier.doi | 10.1172/JCI18212 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A01829 | - |
dc.relation.journalcode | J01322 | - |
dc.identifier.eissn | 1558-8238 | - |
dc.identifier.pmid | 14597764 | - |
dc.subject.keyword | 14597764 | - |
dc.contributor.alternativeName | Paik, Yong Han | - |
dc.contributor.affiliatedAuthor | Paik, Yong Han | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 112 | - |
dc.citation.number | 9 | - |
dc.citation.startPage | 1383 | - |
dc.citation.endPage | 1394 | - |
dc.identifier.bibliographicCitation | JOURNAL OF CLINICAL INVESTIGATION, Vol.112(9) : 1383-1394, 2003 | - |
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