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Mycophenolic acid inhibits oleic acid-induced mesangial cell activation through both cellular reactive oxygen species and inosine monophosphate dehydrogenase 2 pathways

DC Field Value Language
dc.contributor.author허규하-
dc.contributor.author김순일-
dc.contributor.author김유선-
dc.contributor.author주만기-
dc.date.accessioned2015-04-24T16:26:33Z-
dc.date.available2015-04-24T16:26:33Z-
dc.date.issued2009-
dc.identifier.issn0931-041X-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/103519-
dc.description.abstractThe synthesis of extracellular matrix (ECM) in mesangial cells (MCs) plays important roles in the development and progression of renal diseases, including chronic allograft nephropathy. Mycophenolic acid (MPA), an inhibitor of inosine monophosphate dehydrogenase 2 (IMPDH2), suppresses MC proliferation and ECM synthesis. However, the exact inhibitory mechanism of MPA on MCs has not been clearly elucidated. In this study we compared the inhibitory effects of MPA and IMPDH2 reduction [by using small interfering RNA (siRNA)] on oleic acid (OA)-induced fibronectin secretion and cellular reactive oxygen species (ROS) in mouse MCs. Growth-arrested MCs were stimulated with OA in the presence or absence of MPA, IMPDH2 siRNA, N-acetylcysteine (NAC), transforming growth factor beta (TGF-beta) antibody or exogenous guanosine. Fibronectin secretion into the medium was examined by Western blot, dichlorodihydrofluorescein (DCF)-sensitive cellular ROS by fluorescence-activated cell scanning (FACS), TGF-beta levels in the media by enzyme-linked immunosorbent assay (ELISA). OA increased fibronectin secretion, TGF-beta and cellular ROS levels. A TGF-beta neutralizing antibody effectively suppressed OA-induced fibronectin secretion. NAC and MPA completely suppressed OA-induced fibronectin secretion and decreased the levels of TGF-beta and cellular ROS. However, IMPDH2 siRNA partly inhibited OA-induced MC activation. Exogenous guanosine successfully reversed the inhibitory effects of IMPDH2 siRNA on OA-induced MC activation. Pleiotropic inhibitory effect of MPA on OA-induced mouse MC activation was mediated via its antioxidant effect on cellular ROS production and partly via inhibition of IMPDH2 itself. Our results implicate ROS as an alternative therapeutic target for the prevention of hyperlipidemia-related glomerulopathy, chronic allograft nephropathy, and subsequent graft loss.-
dc.description.statementOfResponsibilityopen-
dc.format.extent737~745-
dc.relation.isPartOfPEDIATRIC NEPHROLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAcetylcysteine/pharmacology-
dc.subject.MESHAnimals-
dc.subject.MESHAntibodies, Blocking/pharmacology-
dc.subject.MESHCells, Cultured-
dc.subject.MESHCulture Media, Conditioned/chemistry-
dc.subject.MESHCulture Media, Conditioned/metabolism-
dc.subject.MESHDrug Antagonism-
dc.subject.MESHEnzyme Inhibitors/pharmacology*-
dc.subject.MESHFibronectins/drug effects*-
dc.subject.MESHFibronectins/genetics-
dc.subject.MESHFibronectins/metabolism-
dc.subject.MESHGuanosine/pharmacology-
dc.subject.MESHIMP Dehydrogenase/antagonists & inhibitors*-
dc.subject.MESHIMP Dehydrogenase/genetics-
dc.subject.MESHIMP Dehydrogenase/metabolism-
dc.subject.MESHMesangial Cells/drug effects*-
dc.subject.MESHMesangial Cells/metabolism-
dc.subject.MESHMice-
dc.subject.MESHMice, Transgenic-
dc.subject.MESHMycophenolic Acid/pharmacology*-
dc.subject.MESHOleic Acid/pharmacology*-
dc.subject.MESHRNA Interference/drug effects-
dc.subject.MESHRNA, Small Interfering/pharmacology-
dc.subject.MESHReactive Oxygen Species/metabolism-
dc.subject.MESHTransforming Growth Factor beta/immunology-
dc.titleMycophenolic acid inhibits oleic acid-induced mesangial cell activation through both cellular reactive oxygen species and inosine monophosphate dehydrogenase 2 pathways-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Surgery (외과학)-
dc.contributor.googleauthorKyu Ha Huh-
dc.contributor.googleauthorHyung Joon Ahn-
dc.contributor.googleauthorJehyun Park-
dc.contributor.googleauthorMan Ki Ju-
dc.contributor.googleauthorJae Sook Song-
dc.contributor.googleauthorMyoung Soo Kim-
dc.contributor.googleauthorSoon Il Kim-
dc.contributor.googleauthorYu Seun Kim-
dc.identifier.doi10.1007/s00467-008-1075-8-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA04344-
dc.contributor.localIdA00649-
dc.contributor.localIdA00785-
dc.contributor.localIdA03949-
dc.relation.journalcodeJ02488-
dc.identifier.eissn1432-198X-
dc.identifier.pmid19093139-
dc.identifier.urlhttp://link.springer.com/article/10.1007%2Fs00467-008-1075-8-
dc.subject.keywordMycophenolic acid-
dc.subject.keywordChronic allograft nephropathy-
dc.subject.keywordMesangial cell-
dc.subject.keywordInosine monophosphate dehydrogenase 2-
dc.subject.keywordOleic acid-
dc.subject.keywordHyperlipidemia-
dc.subject.keywordExtracellular matrix-
dc.subject.keywordReactive oxygen species-
dc.contributor.alternativeNameHuh, Kyu Ha-
dc.contributor.alternativeNameKim, Soon Il-
dc.contributor.alternativeNameKim, Yu Seun-
dc.contributor.alternativeNameJoo, Man Ki-
dc.contributor.affiliatedAuthorHuh, Kyu Ha-
dc.contributor.affiliatedAuthorKim, Soon Il-
dc.contributor.affiliatedAuthorKim, Yu Seun-
dc.contributor.affiliatedAuthorJoo, Man Ki-
dc.citation.volume24-
dc.citation.number4-
dc.citation.startPage737-
dc.citation.endPage745-
dc.identifier.bibliographicCitationPEDIATRIC NEPHROLOGY, Vol.24(4) : 737-745, 2009-
dc.identifier.rimsid36061-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers

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