Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
Thrombin‐induced CCN2 expression in human lung fibroblasts requires the c‐Src/JAK2/STAT3 pathway | |
关键词: inflammation; transcription factors; gene regulation; signal transduction; lung; | |
DOI : 10.1189/jlb.0911449 | |
学科分类:生理学 | |
来源: Federation of American Societies for Experimental Biology | |
【 摘 要 】
ThrombinisamultifunctionalserineproteaseandanimportantfibroticmediatorthatinducesCCN2expression.WepreviouslyshowedthatthrombininducesCCN2expressionviaanASK1‐dependentJNK/AP‐1pathwayinhumanlungfibroblasts.Inthisstudy,wefurtherinvestigatedtherolesofc‐Src,JAK2,andSTAT3inthrombin‐inducedCCN2expression.Thrombin‐inducedCCN2expressionandCCN2‐LucactivitywereattenuatedbyaJAKinhibitor(AG490)andJAK2DN,STAT3DN,andtheSTATdecoyODN.Moreover,transfectionofcellswithaCCN2‐mtSTAT‐Lucconstructinhibitedthrombin‐inducedCCN2‐Lucactivity.TreatmentofcellswiththrombincausedJAK2phosphorylationatTyr1007/1008andSTAT3phosphorylationatTyr705intime‐dependentmanners.Thrombin‐inducedSTAT3phosphorylationwasinhibitedbyAG490andJAK2DN.Thrombin‐inducedSTAT3bindingtotheCCN2promoterwasanalyzedbyaDNA‐bindingaffinitypull‐downassay.Inaddition,thrombin‐inducedCCN2expressionandCCN2‐Lucactivitywereinhibitedbyc‐SrcDNandPP2(anSrcinhibitor).Transfectionofcellswithc‐SrcDNalsoinhibitedthrombin‐inducedJAK2andSTAT3phosphorylation.Takentogether,theseresultsindicatethatthrombinmightactivatec‐SrctoinduceJAK2activation,whichinturn,causesSTAT3activation,andfinallyinducesCCN2expressioninhumanlungfibroblasts...
【 授权许可】
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