Cell Signals Influencing Hepatic Fibrosis英文文献资料.docVIP

HindawiPublishingCorporation InternationalJournalofHepatology Volume2012,ArticleID158547,18pages doi:10.1155/2012/158547 ReviewArticle CellSignalsIn?uencingHepaticFibrosis MinCong,KeikoIwaisako,ChunyanJiang,andTatianaKisseleva DepartmentofMedicine,SchoolofMedicine,UniversityofCalifornia,SanDiego,LaJolla,CA92093,USA CorrespondenceshouldbeaddressedtoTatianaKisseleva,tkisseleva@ Received1March2012;Accepted1June2012 AcademicEditor:MichaelOtt Copyright?2012MinCongetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense, whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited. Liver?brosisistheresultoftheentireorganismrespondingtoachronicinjury.Everycelltypeinthelivercontributestothe?brosis. Thispaper?rstdiscusseskeyintracellularsignalingpathwaysthatareinducedduringliver?brosis.Thepaperthenexaminesthe e?ectsofthesesignalingpathwaysonthemajorcelltypesintheliver.Thiswillprovideinsightsintothemolecularpathophysiology ofliver?brosisandshouldidentifytherapeutictargets. 1.Introduction retainaquiescentphenotype(qHSCs),butfollowingTGF- β1stimulation,PDGF,ormatrixsti?ness,orother?brogenic stimulitheyrapidlyactivateintotypeIcollagen,α-smooth muscleactinexpressingmyo?broblasts(aHSCs)[1,4,6].In additiontoHSCs,cholestaticliverinjury causesactivation ofportal?broblasts,whichdi?erentiateintomyo?broblasts andcontributetoscarformation[7,8].Cholestaticinjury also triggers cholangiocyte activation, and proliferation of thebileducts(ductularreaction)[1]. Fibrosisistheoutcomeofmanychronicliverdiseases[1], includinghepatitisBvirus(HBV),hepatitisCvirus(HCV), alcoholic liver disease, and nonalcoholic steatohepatitis (NASH), liver intoxication (drug or nutritionally related) [1].Itismanifestedbymassiveaccumulationoftheextra- cellular matrix (ECM) and scar formation. Several injury- triggering events play a critical role in the pathogenesis of liver ?brosis. Chronic liver injury damages the endothelial barrier and in