Gene Expression Profiling in the Type 1 Diabetes Rat Diaphragm 英文参考文献.docVIP

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Gene Expression Profiling in the Type 1 Diabetes Rat Diaphragm 英文参考文献.doc

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Gene Expression Profiling in the Type 1 Diabetes Rat Diaphragm 英文参考文献

GeneExpressionProfilingintheType1DiabetesRat Diaphragm ErikvanLunteren*,MichelleMoyer Pulmonary,CriticalCareandSleepDivision,DepartmentofMedicine,LouisStokesClevelandDepartmentofVeteransAffairsMedicalCenterandCaseWesternReserve University,Cleveland,Ohio,UnitedStatesofAmerica Abstract Background:Respiratorymusclecontractileperformanceisimpairedbydiabetes,mechanismsofwhichincludedaltered carbohydrate and lipid metabolism, oxidative stress and changes in membrane electrophysiology. The present study examinedtowhatextentthesecellularperturbationsinvolvechangesingeneexpression. Methodology/PrincipalFindings:Diaphragmmusclefromstreptozotocin-diabeticratswasanalyzedwithAffymetrixgene expressionarrays.Diaphragmfromdiabeticratshad105geneswithatleast62-foldsignificantlychangedexpression(55 increased,50decreased),andthesewereassignedtogeneontologygroupsbasedonover-representationanalysisusing DAVID software. There was increased expression of genes involved in palmitoyl-CoA hydrolase activity (a component of lipidmetabolism)(P=0.037,n=2genes,foldchange4.2to27.5)andreducedexpressionofgenesrelatedtocarbohydrate metabolism(P=0.000061,n=8genes,foldchange22.0to28.5).Othergeneontologygroupsamongupregulatedgenes wereproteinubiquitination(P=0.0053,n=4,foldchange2.2to3.4),oxidoreductaseactivity(P=0.024,n=8,foldchange 2.1 to 6.0), and morphogenesis (P=0.012, n=10, fold change 2.1 to 4.3). Other downregulated gene groups were extracellular region (including extracellular matrix and collagen) (P=0.00032, n=13, fold change 22.2 to 23.7) and organogenesis(P=0.032,n=7,foldchange22.1to23.7).Real-timePCRconfirmedthedirectionalityofchangesingene expressionfor30of31genestested. Conclusions/Significance: These data indicate that in diaphragm muscle type 1 diabetes increases expression of genes involved in lipid energetics, oxidative stress and protein ubiquitination, decreases expression of genes involved in carbohydrate metabolism, and has little effect on expression of ion channel genes. Recipr