| Objective:Biliary Epithelial Cells(BECs) is a cell population which has high oxygen consumption,hypermetabolism and is easy to be damaged.It has been long recognized that biliary fibrogenesis is one of the decisive events after ischemic bile duct injury.Despite this,the cell origin of biliary fibrosis remained largely undefined.The aim of this study is to investigate the Epithelial -Mesenchymal Transition of BECs induced by TGF-βand the reversion effect of BMP-7 on EMT.Methods:Isolation and culture of human and rat primary BECs.Recombinant human TGF-βwas added to the cell culture.After 48 hours,TGF-βwas changed to recombinant human BMP-7.Immunofluorescence and immunohistochemical staining were performed on the BECs.Results:1.The BECs of human and rats were successfully isolated,cultured and identified.2.In vitro experiments show that BECs coexpress both the epithelial marker(E-cadherin,CK-19 andβ-catenin) and the myofibroblast marker (Vimentin,S100A4 and Fibronectin) after incubation with fibrogenic TGF-β.3. Incubation of human or rats BECs with BMP-7 significantly reduced the myofibroblast marker expression induced by TGF-β.BMP-7 could reverse the TGF-βmedicated BECs EMT in vitro.Conclusion:BECs may represent a potential avenue to generate myofibroblasts in response to TGF-β,thereby playing an important role in the pathogenesis of hepatic fibrosis.This study suggests that BMP-7 acts as a negative regulator of EMT that prevents BECs from undergoing phenotypic transition.Although the effects of BMP-7 that mediates growth and differentiation of many different cell types have been recognized,the present study unravels a novel mechanism by which BMP-7 elicits its beneficial action on BECs.In this regard,the present study not only underscores that the blockade of EMT is a novel strategy for prevention of injury of BECs but also sets a foundation for the rational utilization of BMP-7 in combating ischemic cholangiopathy.
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