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NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis

DC Field Value Language
dc.contributor.author백용한-
dc.date.accessioned2015-07-15T16:46:19Z-
dc.date.available2015-07-15T16:46:19Z-
dc.date.issued2003-
dc.identifier.issn0021-9738-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/113568-
dc.description.abstractAngiotensin 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.statementOfResponsibilityopen-
dc.format.extent1383~1394-
dc.relation.isPartOfJOURNAL OF CLINICAL INVESTIGATION-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAngiotensin II/pharmacology*-
dc.subject.MESHAnimals-
dc.subject.MESHCells, Cultured-
dc.subject.MESHDNA/metabolism-
dc.subject.MESHEnzyme Activation-
dc.subject.MESHHumans-
dc.subject.MESHLipid Peroxidation/drug effects-
dc.subject.MESHLiver/cytology*-
dc.subject.MESHLiver/drug effects-
dc.subject.MESHLiver/metabolism-
dc.subject.MESHLiver Cirrhosis, Experimental/etiology*-
dc.subject.MESHMice-
dc.subject.MESHMice, Inbred C57BL-
dc.subject.MESHMitogen-Activated Protein Kinases/physiology-
dc.subject.MESHNADPH Oxidases/physiology*-
dc.subject.MESHPhosphoproteins/physiology-
dc.subject.MESHReactive Oxygen Species-
dc.subject.MESHSignal Transduction/physiology*-
dc.subject.MESHTranscription Factor AP-1/metabolism-
dc.titleNADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학)-
dc.contributor.googleauthorRamón Bataller-
dc.contributor.googleauthorRobert F. Schwabe-
dc.contributor.googleauthorDavid A. Brenner-
dc.contributor.googleauthorJohn J. Lemasters-
dc.contributor.googleauthorCurt H. Hagedorn-
dc.contributor.googleauthorRobert Schoonhoven-
dc.contributor.googleauthorTing Qian-
dc.contributor.googleauthorJeffrey Lindquist-
dc.contributor.googleauthorYong Han Paik-
dc.contributor.googleauthorLiu Yang-
dc.contributor.googleauthorYoukyung H. Choi-
dc.identifier.doi10.1172/JCI18212-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA01829-
dc.relation.journalcodeJ01322-
dc.identifier.eissn1558-8238-
dc.identifier.pmid14597764-
dc.subject.keyword14597764-
dc.contributor.alternativeNamePaik, Yong Han-
dc.contributor.affiliatedAuthorPaik, Yong Han-
dc.rights.accessRightsfree-
dc.citation.volume112-
dc.citation.number9-
dc.citation.startPage1383-
dc.citation.endPage1394-
dc.identifier.bibliographicCitationJOURNAL OF CLINICAL INVESTIGATION, Vol.112(9) : 1383-1394, 2003-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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