血管紧张素ⅱ通过p38mapk jnk和jak2信号通路促进大鼠骨髓间充质干细胞向角质细胞分化-angiotensin ⅱ promotes differentiation of rat bone marrow mesenchymal stem cells into keratinocytes through p 38 mapk jnk and jak 2 signaling pathways.docxVIP

血管紧张素II通过p38MAPK、JNK和JAK2信号通路促进大鼠骨髓间充质干细胞向角质细胞分化中文摘要研究目的探讨血管紧张素II（AngiotensinII，AngII）对骨髓间充质干细胞（BoneMesenchymalStemCells，BMSCs）向角质细胞分化的影响及其信号机制，探究血管紧张素II促进创面愈合的机制。研究方法1．分离培养正常Wistar大鼠BMSCs。2．流式细胞仪检法检测BMSCs表面抗原的表达。3.BMSCs多向分化能力的鉴定。4．酶联免疫吸附试验测定BMSCs中AngII分泌浓度。5．免疫细胞化学法测定成角质诱导后BMSCs中角蛋白10的表达。6．流式细胞仪法检测AngII、Losartan、PD123319及其下游信号分子阻滞剂对BMSCs成角质诱导后角蛋白10阳性细胞数的影响。研究结果流式细胞仪检测BMSCs表面标志CD29和CD90阳性表达率均在99%及以上，CD34、CD45阳性表达率均小于2%。AngII在细胞上清液中的浓度随培养时间增加呈递增趋势（P0.05）。流式细胞仪检测添加AngII的成角质诱导组中BMSCs的K10阳性百分率在7d和14d分别为69.02%和82.1%明显高于对照组（P0.05）。而添加Losartan，及下游信号分子阻滞剂SB203580、AG490、SP600125后，K10阳性细胞数减少(P0.05)。结论AngII可显著提高BMSCs向角质细胞的转化率，P38MAPK、JAK2、JNK信号通路与AngII介导的作用密切相关。AngII促进BMSCs向角质细胞转化可能是其促进创面上皮化的机制之一。关键词骨髓间充质干细胞；血管紧张素II；角质细胞；创面愈合IAngiotensinIIPromotesTheDifferentiationOfRatBoneMarrowMesenchymalStemCellsIntoKeratinocytesThroughP38mapk,JNKAndJAK2SignalingPathwaysAbstractBackgroundAngiotensinisanimportanttypeofbiologicalhormonesubstanceinthebody,involvinginregulatingavarietyofrelatedphysiologicalactivities.Asthemostimportanteffectorproteinintherenin-angiotensinsystem,AngiotensinIIplaysacorrespondingphysiologicalrolethroughthebody’sownsecretionandrelease;anditcaninducethedifferentiationofmultipleadultstemcells,especiallyinmesenchymalstemcells.TheeffectofAngIIonMSCsanditssignificanceinwoundhealingwerenotcompletelyunderstood.Objective:ToinvestigatetheeffectofAngiotensinIIonthedifferentiationofbonemarrowmesenchymalstemcellsintokeratinocyteanditssignalmechanism.Methods:TheBMSCsfromWistarratwereisolated.TheexpressionsofBMSCssurfaceantigensweredetectedbyflowcytometrymethod.ThesecretionconcentrationofAngIIwasdetectedbyELISA.Theexpressionofkeratin10(K10)wasdetectedbyimmunocytochemistryafterkeratinocyteinduction.TheeffectsofAngII,Losartan,PD123319andtheirdownstreamsignalmoleculeblockeronthenumberofK10positivecellsafterkeratinocyteinductionbyBMSCswereobserved.Result:ThepositiveratesofBMSCssurfacemarkersCD29andCD90were99%orabove.ThepositiveratesofCD34andCD45werelessthan2%.TheconcentrationofAngII