銀屑病發(fā)病機制及皮膚間充質干細胞治療的研究.pdf

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

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