Periductal bile acid exposure causes cholangiocyte injury and fibrosis.
<h4>Introduction</h4>Bile duct integrity is essential for the maintenance of the structure and function of the biliary tree. We previously showed that cholangiocyte injury in a toxic model of biliary atresia leads to increased monolayer permeability. Increased epithelial permeability was...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0265418 |
| _version_ | 1797974364285566976 |
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| author | Miri Dotan Sophia Fried Adi Har-Zahav Raanan Shamir Rebecca G Wells Orith Waisbourd-Zinman |
| author_facet | Miri Dotan Sophia Fried Adi Har-Zahav Raanan Shamir Rebecca G Wells Orith Waisbourd-Zinman |
| author_sort | Miri Dotan |
| collection | DOAJ |
| description | <h4>Introduction</h4>Bile duct integrity is essential for the maintenance of the structure and function of the biliary tree. We previously showed that cholangiocyte injury in a toxic model of biliary atresia leads to increased monolayer permeability. Increased epithelial permeability was also shown in other cholangiopathies. We hypothesized that after initial cholangiocyte injury, leakage of bile acids into the duct submucosa propagates cholangiocyte damage and fibrosis. We thus aimed to determine the impact of bile acid exposure on cholangiocytes and the potential therapeutic effect of a non-toxic bile acid.<h4>Materials and methods</h4>Extrahepatic bile duct explants were isolated from adult and neonatal BALB/c mice. Explants were cultured with or without glycochenodeoxycholic acid and ursodeoxycholic acid. They were then fixed and stained.<h4>Results</h4>Explants treated with glycochenodeoxycholic acid demonstrated cholangiocyte injury with monolayer disruption and partial lumen obstruction compared to control ducts. Masson's trichrome stains revealed increased collagen fibers. Myofibroblast marker α-SMA stains were significantly elevated in the periductal region. The addition of ursodeoxycholic acid resulted in decreased cholangiocyte injury and reduced fibrosis.<h4>Conclusions</h4>Bile acid leakage into the submucosa after initial cholangiocyte injury may serve as a possible mechanism of disease propagation and progressive fibrosis in cholangiopathies. |
| first_indexed | 2024-04-11T04:18:51Z |
| format | Article |
| id | doaj.art-cf65d4c513ff4b399f7e97ca916fd777 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-11T04:18:51Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-cf65d4c513ff4b399f7e97ca916fd7772022-12-31T05:32:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01173e026541810.1371/journal.pone.0265418Periductal bile acid exposure causes cholangiocyte injury and fibrosis.Miri DotanSophia FriedAdi Har-ZahavRaanan ShamirRebecca G WellsOrith Waisbourd-Zinman<h4>Introduction</h4>Bile duct integrity is essential for the maintenance of the structure and function of the biliary tree. We previously showed that cholangiocyte injury in a toxic model of biliary atresia leads to increased monolayer permeability. Increased epithelial permeability was also shown in other cholangiopathies. We hypothesized that after initial cholangiocyte injury, leakage of bile acids into the duct submucosa propagates cholangiocyte damage and fibrosis. We thus aimed to determine the impact of bile acid exposure on cholangiocytes and the potential therapeutic effect of a non-toxic bile acid.<h4>Materials and methods</h4>Extrahepatic bile duct explants were isolated from adult and neonatal BALB/c mice. Explants were cultured with or without glycochenodeoxycholic acid and ursodeoxycholic acid. They were then fixed and stained.<h4>Results</h4>Explants treated with glycochenodeoxycholic acid demonstrated cholangiocyte injury with monolayer disruption and partial lumen obstruction compared to control ducts. Masson's trichrome stains revealed increased collagen fibers. Myofibroblast marker α-SMA stains were significantly elevated in the periductal region. The addition of ursodeoxycholic acid resulted in decreased cholangiocyte injury and reduced fibrosis.<h4>Conclusions</h4>Bile acid leakage into the submucosa after initial cholangiocyte injury may serve as a possible mechanism of disease propagation and progressive fibrosis in cholangiopathies.https://doi.org/10.1371/journal.pone.0265418 |
| spellingShingle | Miri Dotan Sophia Fried Adi Har-Zahav Raanan Shamir Rebecca G Wells Orith Waisbourd-Zinman Periductal bile acid exposure causes cholangiocyte injury and fibrosis. PLoS ONE |
| title | Periductal bile acid exposure causes cholangiocyte injury and fibrosis. |
| title_full | Periductal bile acid exposure causes cholangiocyte injury and fibrosis. |
| title_fullStr | Periductal bile acid exposure causes cholangiocyte injury and fibrosis. |
| title_full_unstemmed | Periductal bile acid exposure causes cholangiocyte injury and fibrosis. |
| title_short | Periductal bile acid exposure causes cholangiocyte injury and fibrosis. |
| title_sort | periductal bile acid exposure causes cholangiocyte injury and fibrosis |
| url | https://doi.org/10.1371/journal.pone.0265418 |
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