MicroRNA‐16 affects key functions of human endothelial progenitor cells

[摘要] ThecapacityofEPCstorepairinjuredtissuesislimited.TheroleofmiRNAsinEPCsislargelyunknown.WetestedwhethermiRNAsmaybeusefultoenhancetheregenerativecapacityofEPCs.EarlyEPCswereisolatedfromhumanPBMCs,andlateEPCswereamplifiedfromenrichedhumanperipheralCD34+cells.ExpressionprofilesofmiRNAsandmRNAswereobtainedbymicroarrays.AmongthemiRNAsdifferentiallyexpressedbetweenearlyandlateEPCs,fivemembersofthemiR‐16family(miR‐15a/‐15b/‐16/‐103/‐107)wereoverexpressedinearlyEPCs.Web‐accessibledatabasespredicted375genetargetsforthesefivemiRNAs.Amongthese,tworegulatorsofcellcycleprogression(CCND1andCCNE1)andoneassociatedgene(CDK6)werelessexpressedinearlyEPCs.Administrationofanti‐miR‐16inearlyEPCsenhancedtheexpressionofthesethreegenes,andadministrationofpre‐miR‐16inlateEPCsdecreasedtheirexpression.InearlyEPCs,antagonismofmiR‐16allowedforcell‐cyclere‐entry,stimulateddifferentiation,enhancedIL‐8secretion,andpromotedtheformationofcapillary‐likestructuresbyHUVECs.Inconclusion,miR‐16regulateskeybiologicalpathwaysinEPCs.ThismayhaveimportantimplicationstoenhancethecapacityofEPCstorepairinjuredtissues...

[学科分类] 生理学

[关键词] transcriptomic;microarrays;cell cycle;cell differentiation