Snail Involves in the Transforming Growth Factor β1-Mediated Epithelial-Mesenchymal Transition of Retinal Pigment Epithelial Cells 英文参考文献.docVIP

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Snail Involves in the Transforming Growth Factor β1-Mediated Epithelial-Mesenchymal Transition of Retinal Pigment Epithelial Cells 英文参考文献.doc

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Snail Involves in the Transforming Growth Factor β1-Mediated Epithelial-Mesenchymal Transition of Retinal Pigment Epithelial Cells 英文参考文献

SnailInvolvesintheTransformingGrowthFactorb1- MediatedEpithelial-MesenchymalTransitionofRetinal PigmentEpithelialCells HuiLi1,HongweiWang2,FangWang3*,QingGu1,XunXu1 1Department ofOphthalmology,ShanghaiFirstPeople’sHospital,AffiliateofShanghaiJiaotongUniversity,Shanghai,China, 2DepartmentofMedicine,Universityof Chicago,Chicago,Illinois,UnitedStatesofAmerica,3DepartmentofOphthalmology,ShanghaiTenthPeople’sHospital,AffiliateofTongjiUniversity,Shanghai,China Abstract Background:Theproliferationofretinalpigmentepithelium(RPE)cellsresultingfromanepithelial-mesenchymaltransition (EMT)playsakeyroleinproliferativevitreoretinopathy(PVR),whichleadstocomplexretinaldetachmentandthelossof vision.GenesofSnailfamilyencode thezincfinger transcription factorsthathavebeenreportedtobe essentialin EMT duringembryonicdevelopmentandcancermetastasis.However,thefunctionofSnailinRPEcellsundergoingEMTislargely unknown. Principal Findings: Transforming growth factor beta(TGF-b)-1 resulted in EMT in human RPE cells (ARPE-19), which was characterizedbytheexpecteddecreaseinE-cadherinandZonaoccludin-1(ZO-1)expression,andtheincreaseinfibronectin anda-smoothmuscleactin(a-SMA)expression,aswellastheassociatedincreaseofSnailexpressionatbothmRNAand protein levels. Furthermore, TGF-b1 treatment caused a significant change in ARPE-19 cells morphology, with transition from a typical epithelial morphology to mesenchymal spindle-shaped. More interestingly, Snail silencing significantly attenuated TGF-b1-induced EMT in ARPE-19 cells by decreasing the mesenchymal markers fibronectin and a-SMA and increasingtheepithelialmarkerE-cadherinandZO-1.SnailknockdowncouldeffectivelysuppressARPE-19cellmigration. Finally,SnailwasactivatedinepiretinalmembranesfromPVRpatients.Takentogether,Snailplaysveryimportantrolesin TGF-b-1-inducedEMTinhumanRPEcellsandmaycontributetothedevelopmentofPVR. Significance:SnailtranscriptionfactorplaysacriticalroleinTGF-b1-inducedEMTinhumanRPEcells,whichprovidesdeep insightintoth