Smoothmusclecells(SMCs)canswitchbetweenadifferentiated/contractileandanalternative proliferativephenotype.Thetranscriptionfactorserumresponsefactor(SRF)hasbeenimplicatedinthe regulation ofgeneexpressionprofilesdeterminingbothphenotypes.Whereasstrongevidenceexistsfor a roleofSRFinSMCdifferentiation,thecontributionofSRFtoSMCproliferationislesswelldefined.For primaryhumanvascularSMCsinparticular,existingdataarenon-conclusive.TostudySRFfunctionsin primaryhumanvascularSMCs,weusedansiRNAapproach.siRNA-mediated SRF suppressionaffected the expressionofestablishedSRFtargetgenessuchassmoothmuscle a-actin(ACTA2) or SM22a (TAGLN) anddecreasedbothF-actinformationandcellmigration.Furthermore,SRFknockdowncaused a cell-cyclearrestinG1associatedwithreducedhyperphosphorylatedpRB,cyclinAandSKP2levels, and increasedp27kip1 (CDKN1B)proteinlevels.SRF-depletedcellsexpressedsenescence-associated bgalactosidaseindicatinganirreversibleG1arrest.siRNA-mediatedsuppressionof SKP2 triggered senescencetoasimilarextentasSRFdepletion,indicatingthatSRFknockdown-inducedsenescence may bedependentonadecreaseinSKP2.Thus,SRFisanessentialregulatorofprimaryhumanvascular SMC proliferationandsenescence.InterferingwithSRFfunctionmaythereforebeapromisingstrategy for thetreatmentofhyperproliferativeSMCdisorderssuchasatherosclerosisandin-stentrestenosis.
Proliferation of human primary vascular smooth muscle cells depends on serum response factor / D., Werth; Grassi, Gabriele; N., Konjer; Dapas, Barbara; Farra, Rossella; Giansante, Carlo; R., Kandolf; Guarnieri, Gianfranco; A., Nordheim; O., Heidenreich. - In: EUROPEAN JOURNAL OF CELL BIOLOGY. - ISSN 0171-9335. - STAMPA. - 89/2010:(2010), pp. 216-224. [10.1016/j.ejcb.2009.12.002]
Proliferation of human primary vascular smooth muscle cells depends on serum response factor.
GRASSI, GABRIELE;DAPAS, BARBARA;FARRA, ROSSELLA;GIANSANTE, CARLO;GUARNIERI, GIANFRANCO;
2010-01-01
Abstract
Smoothmusclecells(SMCs)canswitchbetweenadifferentiated/contractileandanalternative proliferativephenotype.Thetranscriptionfactorserumresponsefactor(SRF)hasbeenimplicatedinthe regulation ofgeneexpressionprofilesdeterminingbothphenotypes.Whereasstrongevidenceexistsfor a roleofSRFinSMCdifferentiation,thecontributionofSRFtoSMCproliferationislesswelldefined.For primaryhumanvascularSMCsinparticular,existingdataarenon-conclusive.TostudySRFfunctionsin primaryhumanvascularSMCs,weusedansiRNAapproach.siRNA-mediated SRF suppressionaffected the expressionofestablishedSRFtargetgenessuchassmoothmuscle a-actin(ACTA2) or SM22a (TAGLN) anddecreasedbothF-actinformationandcellmigration.Furthermore,SRFknockdowncaused a cell-cyclearrestinG1associatedwithreducedhyperphosphorylatedpRB,cyclinAandSKP2levels, and increasedp27kip1 (CDKN1B)proteinlevels.SRF-depletedcellsexpressedsenescence-associated bgalactosidaseindicatinganirreversibleG1arrest.siRNA-mediatedsuppressionof SKP2 triggered senescencetoasimilarextentasSRFdepletion,indicatingthatSRFknockdown-inducedsenescence may bedependentonadecreaseinSKP2.Thus,SRFisanessentialregulatorofprimaryhumanvascular SMC proliferationandsenescence.InterferingwithSRFfunctionmaythereforebeapromisingstrategy for thetreatmentofhyperproliferativeSMCdisorderssuchasatherosclerosisandin-stentrestenosis.Pubblicazioni consigliate
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