Role of Dlg5lp-dlg, a Membrane-Associated Guanylate Kinase Family Protein, in Epithelial-Mesenchymal Transition in LLc-PK1 Renal Epithelial Cells 英文参考文献.docVIP

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Role of Dlg5lp-dlg, a Membrane-Associated Guanylate Kinase Family Protein, in Epithelial-Mesenchymal Transition in LLc-PK1 Renal Epithelial Cells 英文参考文献.doc

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Role of Dlg5lp-dlg, a Membrane-Associated Guanylate Kinase Family Protein, in Epithelial-Mesenchymal Transition in LLc-PK1 Renal Epithelial Cells 英文参考文献

RoleofDlg5/lp-dlg,aMembrane-AssociatedGuanylate KinaseFamilyProtein,inEpithelial-Mesenchymal TransitioninLLc-PK1RenalEpithelialCells TakuhitoSezaki1.,KohkiInada1.,TakayukiSogabe1,KumiyoKakuda1,LuciaTomiyama1, YohsukeMatsuno1,TakafumiIchikawa1,MichinoriMatsuo1,KazumitsuUeda1,2,NoriyukiKioka1* 1DivisionofAppliedLifeSciences,GraduateSchoolofAgriculture,KyotoUniversity,Sakyo,Kyoto,Japan,2InstituteforIntegratedCell-MaterialSciences(iCeMS),Kyoto University,Sakyo,Kyoto,Japan Abstract Discslargehomolog5(Dlg5)isamemberofthemembrane-associatedguanylatekinaseadaptorfamilyofproteins,someof which are involved in the regulation of epithelial-to-mesenchymal transition (EMT). Dlg5 has been described as a susceptibility gene for Crohn’s disease; however, the physiological function of Dlg5 is unknown. We show here that transforming growth factor-b (TGF-b)-induced EMT suppresses Dlg5 expression in LLc-PK1 cells. Depletion of Dlg5 expressionbyknockdownpromotedtheexpressionofthemesenchymalmarkerproteins,fibronectinanda-smoothmuscle actin,andsuppressedtheexpressionofE-cadherin.Inaddition,activationofJNKandp38,whicharestimulatedbyTGF-b, wasenhancedbyDlg5depletion.Furthermore,inhibitionoftheTGF-breceptorsuppressedtheeffectsofDlg5depletion. TheseobservationssuggestthatDlg5isinvolvedintheregulationofTGF-breceptor-dependentsignalsandEMT. Citation: Sezaki T, Inada K, Sogabe T, Kakuda K, Tomiyama L, et al. (2012) Role of Dlg5/lp-dlg, a Membrane-Associated Guanylate Kinase Family Protein, in Epithelial-MesenchymalTransitioninLLc-PK1RenalEpithelialCells.PLoSONE7(4):e35519.doi:10.1371/journal.pone.0035519 Editor:CaraGottardi,NorthwesternUniversityFeinbergSchoolofMedicine,UnitedStatesofAmerica ReceivedOctober24,2011;AcceptedMarch17,2012;PublishedApril23,2012 Copyright: ? 2012 Sezaki et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcear