銀屑病發(fā)病機制及皮膚間充質(zhì)干細胞治療的研究.pdf

1、上海交通大學(xué)博士學(xué)位論文上海交通大學(xué)博士學(xué)位論文銀屑病發(fā)病機制及皮膚間充質(zhì)干細胞治療的研究銀屑病發(fā)病機制及皮膚間充質(zhì)干細胞治療的研究Pathogenesismechanismunderlyingtreatmentofpsiasiswithskinderivedmesenchymalstemcells作者姓名徐臻堯指導(dǎo)教師王宏林學(xué)科(專業(yè))免疫學(xué)研究生學(xué)號0137109045論文提交日期2016年04月13日研究方向皮膚免疫申請學(xué)位博士學(xué)

2、位培養(yǎng)單位基礎(chǔ)醫(yī)學(xué)院資助基金項目：科技部973項目（2012CB917100），科技部973項目（2014CB541905），國家自然科學(xué)基金重點項目（31330026），國家自然科學(xué)基金青年項目（81202304），國家自然科學(xué)基金重大研究計劃培育項目（91029730），上海教育委員會重點學(xué)科項目（J50208），上海教育委員會重點學(xué)科項目（J50207）。AbstractNF?Bisconstitutivelyactivatedi

3、npsiaticepidermis.HoweverhowactivatedNF?Bpromoteskeratinocytehyperproliferationinpsiasisislargelyunknown.HerewereptthattheNF?BactivationtriggeredbyinflammatycytokinesinducesthetranionofmicrNAmiR31oneofthemostdynamicmicrN

4、Asidentifiedintheskinofpsiaticpatientsmousemodels.GeicdeficiencyofmiR31inkeratinocytesinhibitstheirhyperproliferationdecreasesacanthosisreducesthediseaseseverityinpsiasismousemodels.Furthermeproteinphosphatase6(ppp6c)ane

5、gativeregulatthatrestrictsG1toSphaseprogressionisdiminishedinhumanpsiaticepidermisisdirectlytargetedbymiR31.Theinhibitionofppp6cisfunctionallyimptantfmiR31mediatedbiologicaleffects.MeoveractivatedNF?Binhibitsppp6cexpress

6、iondirectlythroughtheinductionofmiR31enhanceskeratinocyteproliferation.ThusourdataidentifyNF?BinducedmiR31itstargetppp6cascriticalfactsfthehyperproliferationofepidermisinpsiasis.Thestudyaimstoexplethemechanismsofmesenchy

7、malstemcells(MSCs)derivedfromskinofnmalinflammatyconditionftheirtheaputicabilities.WeinvestigatedthechangesoffunctionstherapeuticeffectsonpsiasisbetweenMSCsderivedfromskinofnmalinflammatyconditionsthelatterwasestablished

8、withimiquimod.TheresultsrevealedthatMSCsfromskininflammatymicroenvironmenthadenhancedproliferativemigratycapacities.FuthermethetherapeuticeffectsofMSCsderivedfromIMQtreatedskinweremepotentfthetreatmentofpsiasifmmousemode

9、ls.WhiletheantiapoptosiscapacityofSMSCsafterIMQtreatmentwasdecreased.Insummaryweprovideexperimentalbasisideasftheestablishmentofanewstrategyfthetreatmentofpsiasis.Keywds：psiasismiR31ppp6cmesenchymalstemcells，inflammation