【摘 要】
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Exosomes derived from human umbilical cord mesenchymal stem cells(hUCMSC-Ex)play impor-tant roles in immune and inflammation diseases.However,the role of hUCMSC-Ex in atheroscle-rosis has not been elucidated.In this study,the isolated exosomes were identi
【机 构】
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Department of Emergency Internal Medicine,Shaanxi Provincial People’s Hospital,Xi’an 710068,China;De
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Exosomes derived from human umbilical cord mesenchymal stem cells(hUCMSC-Ex)play impor-tant roles in immune and inflammation diseases.However,the role of hUCMSC-Ex in atheroscle-rosis has not been elucidated.In this study,the isolated exosomes were identified by transmission electron microscopy and nanoparticle tracking analysis.Exosome marker protein levels were increased in the hUCMSC-Ex compared with those in hUCMSC suspension,indicating that exo-somes were successfully isolated from hUCMSCs.Furthermore,eosinophils were treated with oxidized low-density lipoprotein(ox-LDL)to construct inflammation model and then incubated with hUCMSC-Ex derived from hUCMSCs which were transfected with miR-100-5p mimic or miR-100-5p inhibitor.We found that hUCMSC-Ex increased miR-100-5p expression,inhibited cell migration,promoted cell apoptosis,and reduced inflammatory cytokine levels in ox-LDL-treated eosinophils,and miR-100-5p overexpression in hUCMSCs enhanced these effects,while miR-100-5p inhibi-tion reversed these effects.Moreover,frizzled 5(FZD5)was a target gene of miR-100-5p.FZD5 overexpression reversed the inhibitory effects of hUCMSC-Ex-miR-100-5p on cell progression and inflammation in eosinophils.Additionally,hUCMSC-Ex-miR-100-5p decreased the expression of cyclin D1 and β-catenin proteins.Wnt/β-catenin pathway activator BML-284 effectively reversed the effects of hUCMSC-Ex-miR-100-5p on cell progression and inflammation in eosinophils.ApoE-/-mice were fed with high-fat diet to construct an atherosclerosis mice model,and hUCMSC-Ex was injected into mice.hUCMSC-Ex reduced atherosclerotic plaque area and inflammation response in atherosclerosis mice.This study demonstrates that hUCMSC-Ex-miR-100-5p inhibits cell pro-gression and inflammatory response in eosinophils via the FZD5/Wnt/β-catenin pathway,thereby alleviating atherosclerosis progression.
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