Integrins and heparan sulfate proteoglycans on hepatic stellate cells (HSC) are novel receptors for HSC‐derived exosomes

摘要

ExosomesmediateintercellularmicroRNAdeliverybetweenhepaticstellatecells(HSC),theprincipalfibrosis‐producingcellsintheliver.ThepurposeofthisstudywastoidentifyreceptorsonHSCforHSC‐derivedexosomes,whichbindtoHSCratherthantohepatocytes.OurfindingsindicatethatexosomebindingtoHSCisblockedbytreatingHSCwithRGD,EDTA,integrinαvorβ1siRNAs,integrinαvβ3orα5β1neutralizingantibodies,heparin,orsodiumchlorate.Furthermore,exosomecargodeliveryandexosome‐regulatedfunctionsinHSC,includingexpressionoffibrosis‐oractivation‐associatedgenesand/ormiR‐214targetgeneregulation,aredependentoncellularintegrinαvβ3,integrinα5β1,orheparansulfateproteolgycans(HSPG).Thus,integrinsandHSPGmediatethebindingofHSC‐derivedexosomestoHSCaswellasthedeliveryandintracellularactionoftheexosomalpayload...