Response of sinusoidal mouse liver cells to choline-deficient ethionine-supplemented diet 英文参考文献.docVIP
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Response of sinusoidal mouse liver cells to choline-deficient ethionine-supplemented diet 英文参考文献
Ueberhametal.ComparativeHepatology2010,9:8
/content/9/1/8
RESEARCH
OpenAccess
Responseofsinusoidalmouselivercellsto
choline-deficientethionine-supplementeddiet
ElkeUeberham1*,JanB?ttger1,UweUeberham2,4,JensGrosche3,4,RolfGebhardt1
Abstract
Background:Proliferationofovalcells,thebipotentprecursorcellsoftheliver,requiresimpededproliferationand
lossofhepatocytesaswellasaspecificmicro-environment,providedbyadjacentsinusoidalcellsofliver.Despite
theirimmenseimportancefortriggeringtheovalcellresponse,cellsofhepaticsinusoidsarerarelyinvestigated.To
elucidatetheresponseofsinusoidallivercellswehaveemployedacholine-deficient,ethionine-supplemented
(CDE)diet,acommonmethodforinducinganovalcellresponseinrodentliver.Wehaveutilisedselected
expressionmarkerscommonlyusedinthepastforphenotypicdiscriminationofovalcellsandsinusoidalcells:
cytokeratin,E-cadherinandM2-pyruvatekinaseforovalcells;andglialfibrillaryacidicprotein(GFAP)wasusedfor
hepaticstellatecells(HSCs).
Results:CDEdietleadstoanactivationofallcellsofthehepaticsinusoidinthemouseliver.Besideovalcells,also
HSCsandKupffercellsproliferate.Theentirefractionofproliferatingcellsinmouseliveraswellasendothelialcells
andcholangiocytesexpressM2-pyruvatekinase.Concomitantly,GFAP,longconsideredauniquemarkerof
quiescentHSCswasupregulatedinactivatedHSCsandexpressedalsoincholangiocytesandovalcells.
Conclusions:OurresultspointtoanimportantroleofalltypesofsinusoidalcellsinregenerationfromCDE
inducedliverdamageandcallforutmostcautioninusingtraditionalmarkerforidentifyingspecificcelltypes.Thus,
M2-pyruvatekinaseshouldnolongerbeusedforestimatingtheovalcellresponseinmouseliver.CDEdietleads
toactivationofGFAPpositiveHSCsinthepericentralzoneofliverlobulus.Intheperiportalzonethedetectionof
GFAPinbiliarycellsandovalcells,callsothercelltypesasprogenitorsofhepatocytesintoquestionunderCDE
dietconditions.
Background
activated and enrich. For proliferation they require a
Ovalcellreactionoccursunderpathological conditions typical microenvironment wh
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