Altered immunometabolism at the interface of increased endoplasmic reticulum (ER) stress in patients with type 2 diabetes

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: UPR;    inflammation;    miR‐;    146a;    PBMCs;    apoptosis;   

DOI  :  10.1189/jlb.3A1214-609R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ThemechanismofperturbedimmunefunctioninpatientswithT2DMispoorlyunderstood.RecentstudiesimplyaroleforERstressinlinkingimmune‐systemalterationsandmetabolism.Here,weinvestigatedwhetherERstressmarkersanditsdownstreameffectorsignalsarealteredinpatientswithtype2diabetesalongwithproinflammatoryaugmentation.Inourstudy,geneandproteinexpressionofERstressmarkers(GRP‐78,PERK,IRE1α,ATF6,XBP‐1andCHOP)waselevatedsignificantly(P<0.05)inPBMCsfromT2DMpatientscomparedwithcontrolsubjects.ThemRNAexpressionofboththeproinflammatorycytokines(TNF‐αandIL‐6)andoxidativestressmarkers(p22phox,TXNIP,andTRPC‐6;P<0.05)wasalsoincreasedinPBMCsfrompatientswithT2DM.SOCS3mRNAexpressionwasreducedsignificantly(P<0.05)indiabetespatients.mRNAexpressionofmostoftheERstressmarkersfromPBMCscorrelatedsignificantlyandpositivelywithpoorglycemiccontrol,dyslipidemia,IR,andinflammatoryandoxidativestressmarkers.ChronicERstressinPBMCsfrompatientswithT2DMwasevidentfromtheincreasedcaspase‐3activity(P<0.01),whichisanexecutionerofapoptosis.AlongwithanimpairmentofmiR‐146alevels,thedownstreamtargetsofmiR‐146a,viz.,IRAK1andTRAF6mRNAlevels,werealsoelevatedsignificantly(P<0.01)inpatientswithT2DM.TherewasaninverserelationshipamongmiR‐146alevelsandERstressmarkers,inflammatorymarkers,andglycemiccontrol.WedemonstrateevidenceofincreasedERstressmarkerswithimpairedmiR‐146alevelsandincreasedproinflammatorysignalsinpatientswithtype2diabetes...

【 授权许可】

CC BY