RhoA‐mediated signaling up‐regulates hepatocyte growth factor gene and protein expression in response to apoptotic cells

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: macrophage;    PI3K/Akt;    MAPK;   

DOI  :  10.1189/jlb.0710414

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ClearanceofapoptoticcellsbymacrophagesinducesHGFsecretion.WeexaminedtheregulatorymechanismsofHGFmRNAandproteinexpressioninmacrophagesuponexposuretoapoptoticcells.TheinteractionofRAW264.7macrophageswithapoptoticJurkatcells,butnotwithviablecells,resultedinexpressionofHGFmRNAandprotein.ExposureofRAW264.7cellstoapoptoticcellsinducedactivationofRhoA,thePI3K/Aktpathway,andMAPKs,includingp38MAPK,ERK,andJNK.Down‐regulationoftheRhoA/RhokinasepathwaybypharmacologicalinhibitorsoraRhoA‐specificsiRNAsuppressedHGFmRNAandproteinexpressionbymacrophagesinresponsetoapoptoticcellsthroughthephosphorylationofAktandtheMAPKs.InhibitionofPI3KdecreasedphosphorylationofAktandtheMAPKs.InhibitionofJNK,butnotp38MAPKandERK,reducedAktphosphorylation.ThepharmacologicalinhibitorofPI3KandtheMAPKsblockedHGFmRNAandproteinexpression.Othertypesofapoptoticcells,suchasHeLacellsandmurinethymocytes,couldalsoinduceHGFmRNAthroughtheRhoA‐dependentpathway.Likely,theRhoA‐dependentsignalingpathwaywasrequiredforHGFmRNAinductioninprimarycellsofperitonealmacrophagesinresponsetoapoptoticcells.AnHGFR‐blockingantibodydidnotalterapoptoticcell‐inducedactivationofRhoA,Akt,andtheMAPKs,aswellasHGFproduction.Overall,thedataprovideevidencethatactivationoftheRhoA/Rhokinasepathwayup‐regulatestranscriptionalHGFproductioninresponsetoapoptoticcells...

【 授权许可】

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