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High glucose activates the p38 MAPK pathway in cultured human peritoneal mesothelial cells

DC Field Value Language
dc.contributor.author강신욱-
dc.contributor.author김경식-
dc.contributor.author박형천-
dc.contributor.author최규헌-
dc.date.accessioned2015-07-15T17:06:53Z-
dc.date.available2015-07-15T17:06:53Z-
dc.date.issued2003-
dc.identifier.issn0085-2538-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/114255-
dc.description.abstractBACKGROUND: Peritoneal fibrosis is a serious complication in long-term continuous ambulatory peritoneal dialysis (CAPD) patients, but the underlying mechanism is not well understood. Since high glucose activates the p38 mitogen-activated protein kinase (MAPK) pathway in various kinds of cells, and because mesothelial cells are always exposed to high glucose dialysate, we examined the activity and expression of p38 MAPK members in cultured human peritoneal mesothelial cells (HPMCs) under high glucose conditions. METHODS: HPMCs were isolated from omentum and subcultured. After serum restriction, HPMCs were exposed to 5.6 mmol/L glucose (low glucose), 5.6 mmol/L glucose + 34.5 mmol/L mannitol (low glucose + mannitol), or 40 mmol/L glucose (high glucose) for 3 minutes to 48 hours with or without SB203580. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were performed to determine mRNA and protein expression, respectively. RESULTS: p38 MAPK and cyclic adenosine monophosphate (cAMP)-responsive element binding protein (CREB) activities and mRNA expressions were significantly increased in HPMCs exposed to high glucose compared to low glucose or low glucose + mannitol after 10 minutes and remain at higher levels to 48 hours (P < 0.05), but total p38 MAPK and CREB protein expressions did not differ. MAPK kinase 3/6 (MKK3/6) activity and mRNA expression were also higher in high glucose cells after 3 minutes (P < 0.05), and fibronectin mRNA expression was significantly increased in HPMCs exposed to high glucose after 2 hours (P < 0.05). In contrast, high glucose significantly inhibited MAPK phosphatase-1 (MKP-1) protein and mRNA expression after 10 minutes (P < 0.05). SB203580 (1 micromol/L) pretreatment for 1 hour significantly reduced high glucose-induced CREB activity and fibronectin mRNA expression by 89% and 75%, respectively (P < 0.05). CONCLUSION: p38 MAPK activity was increased in HPMCs exposed to high glucose, in parallel with increased MKK3/6 activity and decreased MKP-1 expression, resulting in CREB activation. This activated p38 MAPK pathway may play a role in the pathogenesis of peritoneal fibrosis.-
dc.description.statementOfResponsibilityopen-
dc.relation.isPartOfKIDNEY INTERNATIONAL-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHCalcium-Calmodulin-Dependent Protein Kinases/genetics-
dc.subject.MESHCalcium-Calmodulin-Dependent Protein Kinases/metabolism-
dc.subject.MESHCell Cycle Proteins*-
dc.subject.MESHCyclic AMP Response Element-Binding Protein/genetics-
dc.subject.MESHCyclic AMP Response Element-Binding Protein/metabolism-
dc.subject.MESHDual Specificity Phosphatase 1-
dc.subject.MESHEnzyme Induction/drug effects-
dc.subject.MESHEnzyme Inhibitors/pharmacology-
dc.subject.MESHEpithelial Cells/drug effects-
dc.subject.MESHEpithelial Cells/enzymology*-
dc.subject.MESHFibronectins/biosynthesis-
dc.subject.MESHGlucose/pharmacology*-
dc.subject.MESHHumans-
dc.subject.MESHImidazoles/pharmacology-
dc.subject.MESHImmediate-Early Proteins/genetics-
dc.subject.MESHImmediate-Early Proteins/metabolism-
dc.subject.MESHMAP Kinase Kinase 3-
dc.subject.MESHMAP Kinase Kinase 6-
dc.subject.MESHMAP Kinase Signaling System/drug effects-
dc.subject.MESHMitogen-Activated Protein Kinase Kinases/genetics-
dc.subject.MESHMitogen-Activated Protein Kinase Kinases/metabolism-
dc.subject.MESHMitogen-Activated Protein Kinases/genetics-
dc.subject.MESHMitogen-Activated Protein Kinases/metabolism*-
dc.subject.MESHPeritoneum/cytology*-
dc.subject.MESHPeritoneum/enzymology-
dc.subject.MESHPhosphoprotein Phosphatases*-
dc.subject.MESHProtein Phosphatase 1-
dc.subject.MESHProtein Tyrosine Phosphatases/genetics-
dc.subject.MESHProtein Tyrosine Phosphatases/metabolism-
dc.subject.MESHProtein-Tyrosine Kinases/genetics-
dc.subject.MESHProtein-Tyrosine Kinases/metabolism-
dc.subject.MESHPyridines/pharmacology-
dc.subject.MESHRNA, Messenger/analysis-
dc.subject.MESHp38 Mitogen-Activated Protein Kinases-
dc.titleHigh glucose activates the p38 MAPK pathway in cultured human peritoneal mesothelial cells-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Surgery (외과학)-
dc.contributor.googleauthorZhong-Gao Xu-
dc.contributor.googleauthorKyung Sik Kim-
dc.contributor.googleauthorShin-Wook Kang-
dc.contributor.googleauthorDae Suk Han-
dc.contributor.googleauthorHo Yung Lee-
dc.contributor.googleauthorKyu Hun Choi-
dc.contributor.googleauthorHyeong Cheon Park-
dc.identifier.doi10.1046/j.1523-1755.2003.00836.x-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA00053-
dc.contributor.localIdA00299-
dc.contributor.localIdA01759-
dc.contributor.localIdA04043-
dc.relation.journalcodeJ01941-
dc.identifier.eissn1523-1755-
dc.identifier.pmid12631076-
dc.identifier.urlhttps://www.kidney-international.org/article/S0085-2538(15)48963-X/abstract-
dc.subject.keywordperitoneal fibrosis-
dc.subject.keywordhigh glucose-
dc.subject.keywordmesothelial cells-
dc.subject.keywordp38 MAPK-
dc.subject.keywordfibronectin-
dc.contributor.alternativeNameKang, Shin Wook-
dc.contributor.alternativeNameKim, Kyung Sik-
dc.contributor.alternativeNamePark, Hyeong Cheon-
dc.contributor.alternativeNameChoi, Kyu Hun-
dc.contributor.affiliatedAuthorKang, Shin Wook-
dc.contributor.affiliatedAuthorKim, Kyung Sik-
dc.contributor.affiliatedAuthorPark, Hyeong Cheon-
dc.contributor.affiliatedAuthorChoi, Kyu Hun-
dc.rights.accessRightsnot free-
dc.citation.volume63-
dc.citation.number3-
dc.citation.startPage958-
dc.citation.endPage968-
dc.identifier.bibliographicCitationKIDNEY INTERNATIONAL, Vol.63(3) : 958-968, 2003-
dc.identifier.rimsid41867-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers

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