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Mesenchymal Stem-cell-derived Exosomal MiR-145 Inhibits Atherosclerosis By Targeting JAM-A

Posted on:2022-04-17Degree:MasterType:Thesis
Country:ChinaCandidate:W Z YangFull Text:PDF
GTID:2504306566979949Subject:Neurology
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Background: Atherosclerosis is a chronic inflammatory disease associated with the development of plaques that can be converted into an acute clinical event by thrombosis or plaque rupture.Mesenchymal stem cells exhibit therapeutic effects for the treatment of various diseases,including atherosclerosis.Micro RNA is short RNA molecule,which can regulate some important biological procedure.Micro RNAs are unstable in circulation system,for they are easily to be degraded by RNA enzyme.The MSC-derived exosomes,which are believed that can protect and transfer micro RNA.Previous researches also reported various positive effect of MSC-derived exosomes,such as anti-inflammation.Method: We predicted a series of micro RNAs by bioinformatics technology such function enrichment and target prediction.We isolated the huc-MSC by tissue-adherent method from the umbilic cord,the isolated cells were identified by cytometry and immunofluorescence,and the MSC-derived exosomes were identified by western blot,NTA and transmission microscope.The pkh26 fluorescence and cell co-culture technology were used to identify the target relationship between MSC-derived exosomes and HUVECs.In the experiments in vitro,we used western blot,PCR to evaluate the expression of micro RNA-145,JAM-A m RNA and JAM-A protein.In the experiments in vivo,we used H&E stain,immunochemistry to observe the form of atherosclerosis plaque and evaluate the JAM-A expression in plaque tissue.Result: In this study,we show that micro RNA-145(mi R-145)is associated with atherosclerosis by micro RNA sequencing and bioinformatics analysis.MSC-derived mi R-145-rich exosomes could efficiently deliver mi R-145 from MSCs to human umbilical vein endothelial cells.Treatment of mi R-145-rich exosomes could down-regulate JAM-A,inhibit migration in vitro,and reduce atherosclerotic plaque in vivo.Conclusion: Our study suggests that MSC-derived mi R-145-rich exosomes have greatpotential for atherosclerosis prevention.
Keywords/Search Tags:Atherosclerosis, exosome, micro RNA, JAM-A, EC
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