Down‐regulation of survivin alleviates experimental arthritis
[摘要] Survivinisaproto‐oncogenethatregulatescelldivisionandapoptosis.Itisamolecularmarkerofcancer.Recently,survivinhasemergedasafeatureofRA,associatedwithseverejointdamageandpoortreatmentresponse.Thepresentstudyexaminedifinhibitionofsurvivinaffectsexperimentalarthritis,whichwasinducedinmBSA‐immunizedmicebyaninjectionofmBSAinthekneejointordevelopedspontaneouslyincollagentypeII‐immunizedmice.TheinhibitionofsurvivintranscriptionbyalentivirusshRNAconstructalleviatedjointinflammationandreducedbonedamage.Theinhibitionofsurvivinreducedthelevelsofmetalloproteinases,β‐catenin,andvimentin,limitingtheinvasivecapacityofsynovia,whilenoinhibitionofosteoclastogenesiscouldbefound.Theinhibitionofsurvivinledtoap53‐independentreductionofTcellproliferationandfavoredthetranscriptionandactivityofBlimp‐1,whichlimitedIL‐2productionandfacilitatedformationofregulatoryFoxp3+CD4+andeffectorCD8+Tcells.Thestudyshowsthattheinhibitionofsurvivinissufficienttoreducejointinflammationandbonedamageinpreclinicalmodelsofarthritis.Antiarthriticeffectsofsurvivininhibitionarerelatedtop53‐independentcontroloflymphocyteproliferation...
[发布日期] [发布机构]
[效力级别] [学科分类] 生理学
[关键词] T cells;Blimp‐1;p53;Treg;erosions;synovitis [时效性]
