Cellular Senescence in Livers from Children with End Stage Liver Disease 英文参考文献.docVIP

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Cellular Senescence in Livers from Children with End Stage Liver Disease 英文参考文献.doc

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Cellular Senescence in Livers from Children with End Stage Liver Disease 英文参考文献

CellularSenescenceinLiversfromChildrenwithEnd StageLiverDisease GabrielaGutierrez-Reyes1.,MariadelCarmenGarciadeLeon1.,GustavoVarela-Fascinetto2 ,Pedro Valencia2,RuyPe′rezTamayo1,ClaudiaGonzalezRosado1,BlancaFarfanLabonne1,NormaMorales Rochilin1,RosalindaMartinezGarcia1,JonathanAguirreValadez1,GabrielaTognoLatour1,DanaLau Corona1,GuillermoRoblesDiaz1,AlbertZlotnik3,DavidKershenobich1* 1Department of Experimental Medicine, School of Medicine, Universidad Nacional Auto′noma de Me′xico (UNAM), Mexico City, Mexico, 2Department of Surgery and Pathology,HospitalInfantildeMe′xicoFedericoGomez,MexicoCity,Mexico,3UniversityofCaliforniaIrvine,Irvine,California,UnitedStatesofAmerica Abstract Background:Senescentcellsoccurinadultswithcirrhoticliversindependentoftheetiology.Aim:Investigatethepresence rateofcellularsenescenceandexpressionofcellcyclecheckpointsinliversfromchildrenwithendstagedisease. Methodology/PrincipalFindings:Liversoffivechildrenagedthreeyearsorlessundergoinglivertransplantationdueto tyrosinemia (n=1), biliary atresia (n=2), or fulminant hepatitis (n=2) were analyzed for senescence associated b- galactosidase(SA-bgal)activityandp16INK4a,p21cip1andp53.AllliversdisplayedpositivecellularstainingforSA-bgalin the canals of Hering and interlobular biliary ducts. In the presence of cirrhosis (3/5 cases) SA-bgal was found at the cholangioles and hepatocytes surrounding the regenerative nodules. Children with fulminant hepatic failure without cirrhosishadsignificantductulartransformationwithintenseSA-bgalactivity.NoSA-bgalactivitywasevidentinthefibrous septa.Stainingforp53hadasimilardistributiontothatobservedforSA-bgal.Stainingforp16INK4aandp21cip1waspositive intheexplantedliverofthepatientwithtyrosinemia,inthehepatocytes,thecanalsofHering,cholangiolesandinterlobular bileducts.Intheliverswithfulminanthepatitis,p21cip1stainingoccurredintheareasofductulartransformationandinthe interlobularbileducts. Conclusions/Significance:Cellularsenescenceinliversofchildrenwithendsta