Objective To explore the effect of mesenchymal stem cells-derived exosomes(MSCs-Exo)on the aging phenotype of cardiac fibroblasts in elderly mice through and to investigate the key exosomal proteins involved.Methods Exosomes derived from human umbilical cord mesenchymal stem cells were extracted by ultracentrifugation and identified by transmission electron microscopy,nanoparticle tracking analysis and Western blotting.Cardiac fibroblasts were isolated from 18-month-old mice(elderly group)and 4-week-old mice(young group),respectively;and the isolated cardiac fibroblasts were treated with MSC-Exo.Cell senescence markers were detected with β-galactosidase staining,cell viability was determined with CCK-8 method,and cell migration was tested with scratch assay.The protein content of MSCs-Exo was analyzed by bioinformatics methods including GO enrichment and protein-protein interaction analysis based on public databases.The roles of exosome proteins on cell aging were verified by knock-down of potential targets.Results MSCs-Exo significantly down-regulated the expression of the senescence marker β-galactosidase in cardiac fibroblasts of elderly mice,and significantly promoted cell proliferation activity and migration.Bioinformatics analysis showed that P4HA2 in exosomal protein content was possibly a key protein in the collagen fiber tissue pathway with the highest degree of GO enrichment.P4HA2-knockdown MSCs-Exo decreased the alleviating effect on aging of cardiac fibroblasts in elderly mice.Conclusion Mesenchymal stem cell-derived exosomes can exert anti-aging effect,and promote cell proliferation and migration in cardiac fibroblasts of elderly mice,and P4HA2 protein in exosomes may be a core component for such functions.
维普
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