CD47 Regulates Collagen I-Induced Cyclooxygenase-2 Expression and Intestinal Epithelial Cell Migration 英文参考文献.docVIP

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CD47 Regulates Collagen I-Induced Cyclooxygenase-2 Expression and Intestinal Epithelial Cell Migration 英文参考文献.doc

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CD47 Regulates Collagen I-Induced Cyclooxygenase-2 Expression and Intestinal Epithelial Cell Migration 英文参考文献

CD47RegulatesCollagenI-InducedCyclooxygenase-2 ExpressionandIntestinalEpithelialCellMigration OliverJayBroom1,YuanZhang1,Per-ArneOldenborg2,RaminMassoumi1,AnitaSjo¨lander1* 1CellandExperimentalPathology,DepartmentofLaboratoryMedicine,LundUniversity,ClinicalResearchCentre,Malmo¨ UniversityHospital(UMAS),Malmo¨,Sweden, 2DepartmentofIntegrativeMedicalBiology,Umea? University,Umea?, Sweden Abstract Increasedepithelialcellexpressionofthecyclooxgenase-2(COX-2)enzymeisacharacteristiceventofbothinflammatory boweldiseaseandcoloncancer.WeherereportthenovelfindingsthatcollagenI-induceddenovosynthesisofCOX-2in intestinalepithelialcellsisinhibitedbypertussistoxin(PTX)andbyaninhibitorypeptideselectivefortheheterotrimeric Gai3-protein. These findings could be explained by a regulatory involvement of the G-protein-dependent integrin- associated proteinCD47.Insupport ofthis notion,weobservedacollagen I-inducedassociation betweenCD47and a2 integrins. This association was reduced by a blocking anti-CD47 antibody but not by PTX or a control anti-b 2 antibody. Furthermore, a blocking antibody against CD47, dominant negative CD47 or specific siRNA knock down of CD47, significantly reduced collagen I-induced COX-2 expression. COX-2 has previously been shown to regulate intestinal epithelial cell adhesion and migration. Morphological analysis of intestinal cells adhering to collagen I revealed a co- localisationofCD47anda2integrinstonon-apoptoticmembraneblebsenrichedinRhoAandF-actin.TheblockingCD47 antibody,PTXandaselectiveCOX-2inhibitor,dramaticallyinhibitedtheformationoftheseblebs.Inaccordance,migration ofthesecellsonacollagenI-coatedsurfaceorthroughacollagenIgelweresignificantlyreducedbytheCD47blocking antibody,siRNAknockdownofCD47andtheCOX-2inhibitorNS-398.Inconclusion,wepresentnoveldatathatidentifies the G-protein-dependent CD47 protein as a key regulator of collagen I-induced COX-2 expression and a promoter of intestinalepithelialcellmigration. Citation:BroomOJ,ZhangY,O