Monocyte-secreted Wnt5a interacts with FZD5 in microvascular endothelial cells and induces angiogenesis through tissue factor signaling.pdfVIP

380 lJournalofMolecularCellBiology(2014)，6(5)，380—393 doi：10．1O93／jmcb／mjuO36 PublishedonlineSeptember19，2014 Article m C r 0 Monocyte--secretedWnt5ainteractswithFZD5in V ascularendothe|iaIcellsandinduces angl●0geneS●ISthIiroughIitis‘suef一act一orsl·gnaii|in‘g GemmaArderiu ，SoniaEspinosa’EstherPefia，RosaAledo，andLinaBadimon ， CardiovascularResearchCenter(CSIC-~CCC)，Institutd’Investigaci6Biom~dicaSantPau(1iB-SantPau)andUniversitatAut6nomadeBarcelona(UAB)， Barcelona08025。Spain Theseauthorscontributedequallytothiswork． C0rrespOndenceto：LinaBadimon，E-mail：Ibadimon@csic-iccc．org Angiogenesisduringreactiveandpathologicprocessesischaracteristicallyassociatedwithinflammation．Inflammatorycellspartici- pateinangiogenesisbysecretingdifierentmoleculesthataffectendothelialcellfunctions．WehadpreviousIvshownthatinduced tissuefactor(_rF)expressioninactivatedmicrovascularendotheliaIcells(mEt)lsabletoinduceangiogenesisviaautocrineregulation． However。thesignalsthatinduceTFexpressioninmECarenotfuUyknown．Here，wedemonstratethatmonocyteparacrinecross-talk withmECstriggersmEC-TFxe pression．Wehaveldentifiedthatmonocvte-secretedWntSainducesTFxepressioninmECandfunction- allyinducescellmonolayerrepairandangiotubeformation／nvitroaswetIasmicrovesseIformation／nvivo．Monocyte-secretedWntSa activatesFZD5inmECs。whichsignalstoinducethereleaseofintracellu[arCa andincreaseNFKBtranscriptionactivityandTFgene expression．Insum。WntSasecretedbymonocytessignalsthroughthenoncanonicaIWnt-FZD5pathwayinmECstoinduceTFxepres- sionthatinducesangiogenesisbyautocrineregulation． Keywords：wntSa，tissuefactor，microvascularendothelialcells，monocytes，angiogenesis Introduction