就実大学薬学部薬学科分子生物临床诊断学(〒703.pdf

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1、honp.1[100%]YAKUGAKUZASSHI128(2)263―268(2008)2008ThePharmaceuticalSocietyofJapan263―Reviews―炎症性関節リウマチ滑膜細胞のシグナル伝達森宏樹，中西徹SignalTransductionofIn‰ammatorySynoviocytesinRheumatoidArthritisHirokiMORIandTohruNAKANISHIMolecularBiologyandMolecularDiagnosis,ShujitsuUnive

2、rsitySchoolofPharmacy,161Nishigawara,OkayamaCity7038516,Japan(ReceivedAugust22,2007)Recentadvancesinpost-genomictechnologyenableustoanalyzegeneexpressionandproteinmodiˆcationcompre-hensivelyintissuesandcells,resultinginnewdevelopmentsintheanalysisofmolecularev

3、entsofdiseases.Wehavebeenstudyingthepathogenicandprogressivemechanismsofdiseasesfromtheaspectofsignallingpathwaysofcells.In‰am-matorycytokinessuchasTNF-alphaandIL-1producedfromactivatedmacrophagesstimulatetheovergrowthofsyn-oviocytesandinduceosteoclastdiŠerentiat

4、ioninrheumatoidarthritis(RA).Asaconsequence,cartilageandbonedes-tructioninjointsisobservedinRApatients.Recently,thepathogenicmechanismsarebeginningtobediscussedatthemolecularlevel.Forexample,up-regulationofsynoviolin,anER-localizingE3ubiquitinligase,insynoviocyte

5、sisin-volvedinRAbecauserheumatoidsynoviocytesproducesynoviolinandoverexpressionofhumansynoviolininmicecausesarthropathy.Sofarlittleisknownaboutligandsinducingarthropathyandtheirreceptorsinthedisease.Wecharacterizedrheumatoidsynoviocytesbyproˆlinggeneexpressionwit

6、hgenome-wideDNAchips,andfoundthataclusterantigenisinvolvedintheproteinsup-regulatedinrheumatoidsynoviocytes.Wehavebeenanalyzingtherelation-shipbetweensynoviolinexpressionandtheactivationofclusterantigen.Theclusterantigenanditssignalpathwayscouldbecomeanoveltherap

7、eutictargetforRA.WediscussthepossibilityofdirectinductionofsynoviolinexpressionviaactivationofsignalpathwaysdirectedbytheclusterantigeninRAsynoviocytes.Keywords―rheumatoidarthritis;synoviocyte;synoviolin;DNAchip(DNAmicroarray);clusterantigen1.はじめにカインの産生亢進により，滑膜線維

8、芽細胞の活性ゲノム情報を用いたポストゲノム技術の進展によ化・異常増殖あるいは破骨細胞の分化誘導が起こり，最近，組織・細胞内の遺伝子発現・タンパク質る．またその結果，骨・関節破壊及び増殖滑膜の軟修飾などが網羅的に解析できるようになり，種々の骨・骨への進入という主病態を生じる．こうした過病態の分子レベルでの解析に新しい展