Selective Activation of p120ctn-Kaiso Signaling to Unlock Contact Inhibition of ARPE-19 Cells without Epithelial-Mesenchymal Transition 英文参考文献.docVIP

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Selective Activation of p120ctn-Kaiso Signaling to Unlock Contact Inhibition of ARPE-19 Cells without Epithelial-Mesenchymal Transition 英文参考文献.doc

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Selective Activation of p120ctn-Kaiso Signaling to Unlock Contact Inhibition of ARPE-19 Cells without Epithelial-Mesenchymal Transition 英文参考文献

SelectiveActivationofp120ctn-KaisoSignalingtoUnlock ContactInhibitionofARPE-19CellswithoutEpithelial- MesenchymalTransition Hung-ChiChen1,2,3.,Ying-TingZhu1.,Szu-YuChen1,SchefferC.G.Tseng1* 1Tissue Tech, Inc., Ocular Surface Center, and Ocular Surface Research Education Foundation, Miami, Florida, United States of America, 2Department of Ophthalmology,ChangGungMemorialHospital,Linkou,Taiwan,3GraduateInstituteofClinicalMedicalSciences,ChangGungUniversityCollegeofMedicine,Taoyuan, Taiwan Abstract Contact-inhibitionubiquitouslyexistsinnon-transformedcellsandexplainsthepoorregenerativecapacityofinvivohuman retinalpigmentepithelialcells(RPE)duringaging,injuryanddiseases.RPEinjuryordegenerationmayunlockmitoticblock mediated by contact inhibition but may also promote epithelial-mesenchymal transition (EMT) contributing to retinal blindness.Herein,weconfirmedthatEMTensuedinpost-confluentARPE-19cellswhencontactinhibitionwasdisrupted with EGTA followed by addition of EGF and FGF-2 because of activation of canonical Wnt and Smad/ZEB signaling. In contrast, knockdown of p120-catenin (p120) unlocked such mitotic block by activating p120/Kaiso, but not activating canonicalWntandSmad/ZEBsignaling,thusavoidingEMT.NuclearBrdUlabelingwascorrelatedwithnuclearreleaseof Kaisothroughp120nucleartranslocation,whichwasassociatedwithactivationofRhoA-ROCKsignaling,destabilizationof microtubules. Prolonged p120 siRNA knockdown followed by withdrawal further expanded RPE into more compact monolayerswithanormalphenotypeandahigherdensity.Thisnewstrategybasedonselectiveactivationofp120/Kaiso but not Wnt/b-catenin signaling obviates the need of using single cells and the risk of EMT, and may be deployed to engineersurgicalgraftscontainingRPEandothertissues. Citation:ChenH-C,ZhuY-T,ChenS-Y,TsengSCG(2012)SelectiveActivationofp120ctn-KaisoSignalingtoUnlockContactInhibitionofARPE-19Cellswithout Epithelial-MesenchymalTransition.PLoSONE7(5):e36864.doi:10.1371/journal.pone.0036864 Editor:Wei-ChunChin,U