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Experimental models to study cholangiocyte biology

World Journal of Gastroenterology 2002年第1期8卷 1-4页

作者： Pamela S.Tietz Robert C.Huebert anatoliy masyuk Tatyana masyuk Patrick L.Splinter Nicholas F.LaRusso Center for Basic Research in Digestive Diseases Department of Internal Medicine and Biochemistry and Molecular BiologyMayo Medical SchoolClinic and FoundationRochesterMN 55905

Cholangiocytes-the epithelial cells which line the bileducts-are increasingly recognized as importanttransporting epithelia actively involved in the absorptionand secretion of water,ions,and *** is due in part to the recent development ofnew experimental *** biologic concepts haveemerged including the identification and topography ofreceptors and flux proteins on the apical and/orbasolateral membrane which are involved in the molecularmechanisms of ductal bile *** isolatedand/or perfused bile duct units from livers of rats andmice serve as new,physiologically relevant in vitromodels to study cholangiocyte *** treedimensions and novel insights into anatomic remodeling ofproliferating bile ducts have emerged from three-dimensional reconstruction using CT scanning andsophisticated ***,new pathologicconcepts have arisen regarding the interaction ofcholangiocytes with pathogens such as *** concepts and associated methodologiesmay provide the framework to develop new therapies forthe cholangiopathies,a group of important hepatobiliarydiseases in which cholangiocytes are the target cell.

关键词： Animals Bile Ducts Biological Transport Epithelial Cells Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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Differential expression of cholangiocyte and ileal bile acid transporters following bile acid supplementation and depletion

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World Journal of Gastroenterology 2004年第10期10卷 1440-1446页

作者： N.Sertac Kip Konstantinos N.Lazaridis anatoliy I.masyuk Patrick L.Splinter Robert C.Huebert Nicholas F.LaRusso Center for Basic Research in Digestive Diseases Division of Gastroenterology and HepatologyDepartment of Internal MedicineMayo Medical SchoolClinic and FoundationRochesterMN 55905USA

AIM: We have previously demonstrated that cholangiocytes, the epithelial cells lining intrahepatic bile ducts,encode two functional bile acid transporters via alternative splicing of a single gene to facilitate bile acid vectorial transport. Cholangiocytes possess ASBT,an apical sodium-dependent bile acid transporter to take up bile acids,and t-ASBT,a basolateral alternatively spliced and truncated form of ASBT to efflux bile *** hepatocyte and ileal bile acid transporters are in part regulated by the flux of bile acids, the effect of alterations in bile acid flux on the expression of t-ASBT in terminal ileocytes remains ***,we tested the hypothesis that expression of ASBT and t-ASBT in cholangiocytes and ileocytes was regulated by bile acid flux. METHODS: Expression of ASBT and t-ASBT message and protein in cholangiocytes and ileocytes isolated from pair- fed rats given control (C) and 1% taurocholate (TCA) or 5% cholestyramine (CY) enriched diets,were assessed by both quantitative RNase protection assays and quantitative *** data obtained from each of the control groups were pooled to reflect the changes observed following TCA and CY treatments with respect to the control diets. Cholangiocyte taurocholate uptake was determined using a novel microperfusion technique on intrahepatic bile duct units (IBDUs) derived from C,TCA and CY fed rats. RESULTS: In cholangiocytes,both ASBT and t-ASBT message RNA and protein were significantly decreased in response to TCA feeding compared to C *** contrast, message and protein of both bile acid transporters significantly increased following CY feeding compared to C *** the ileum,TCA feeding significantly up-regulated both ASBT and t-ASBT message and protein compared to C diet,while CY feeding significantly down-regulated message and protein of both bile acid transporters compared to C *** anticipated from alterations in cholangiocyte ASBT expression,the uptake of taurocholate in microp

关键词： Cholestyramine dosage Ileum Taurocholic Acid Alternative Splicing Animals Bile Ducts Diet Eating Epithelial Cells Gene Expression Regulation Male Organic Anion Transporters, Sodium-Dependent Protein Isoforms Rats Rats, Inbred F344 Symporters

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