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Dysregulated Bile Transporters and Impaired Tight Junctions During Chronic Liver Injury in Mice.
- Source :
-
Gastroenterology [Gastroenterology] 2018 Oct; Vol. 155 (4), pp. 1218-1232.e24. Date of Electronic Publication: 2018 Jun 30. - Publication Year :
- 2018
-
Abstract
- Background & Aims: Liver fibrosis, hepatocellular necrosis, inflammation, and proliferation of liver progenitor cells are features of chronic liver injury. Mouse models have been used to study the end-stage pathophysiology of chronic liver injury. However, little is known about differences in the mechanisms of liver injury among different mouse models because of our inability to visualize the progression of liver injury in vivo in mice. We developed a method to visualize bile transport and blood-bile barrier (BBlB) integrity in live mice.<br />Methods: C57BL/6 mice were fed a choline-deficient, ethionine-supplemented (CDE) diet or a diet containing 0.1% 3,5-diethoxycarbonyl-1, 4-dihydrocollidine (DDC) for up to 4 weeks to induce chronic liver injury. We used quantitative liver intravital microscopy (qLIM) for real-time assessment of bile transport and BBlB integrity in the intact livers of the live mice fed the CDE, DDC, or chow (control) diets. Liver tissues were collected from mice and analyzed by histology, immunohistochemistry, real-time polymerase chain reaction, and immunoblots.<br />Results: Mice with liver injury induced by a CDE or a DDC diet had breaches in the BBlB and impaired bile secretion, observed by qLIM compared with control mice. Impaired bile secretion was associated with reduced expression of several tight-junction proteins (claudins 3, 5, and 7) and bile transporters (NTCP, OATP1, BSEP, ABCG5, and ABCG8). A prolonged (2-week) CDE, but not DDC, diet led to re-expression of tight junction proteins and bile transporters, concomitant with the reestablishment of BBlB integrity and bile secretion.<br />Conclusions: We used qLIM to study chronic liver injury, induced by a choline-deficient or DDC diet, in mice. Progression of chronic liver injury was accompanied by loss of bile transporters and tight junction proteins.<br /> (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Biological Transport
Chemical and Drug Induced Liver Injury, Chronic blood
Chemical and Drug Induced Liver Injury, Chronic etiology
Chemical and Drug Induced Liver Injury, Chronic pathology
Choline Deficiency complications
Claudins metabolism
Disease Models, Animal
Ethionine
Hepatocytes pathology
Kinetics
Liver pathology
Mice, Inbred C57BL
Permeability
Pyridines
Tight Junctions pathology
Bile metabolism
Chemical and Drug Induced Liver Injury, Chronic metabolism
Hepatocytes metabolism
Liver metabolism
Membrane Transport Proteins metabolism
Tight Junctions metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0012
- Volume :
- 155
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 29964040
- Full Text :
- https://doi.org/10.1053/j.gastro.2018.06.048