Periductal bile acid exposure causes cholangiocyte injury and fibrosis.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2022
2022
Historique:
received:
24
11
2021
accepted:
01
03
2022
entrez:
16
3
2022
pubmed:
17
3
2022
medline:
6
5
2022
Statut:
epublish
Résumé
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. 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. 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. Bile acid leakage into the submucosa after initial cholangiocyte injury may serve as a possible mechanism of disease propagation and progressive fibrosis in cholangiopathies.
Identifiants
pubmed: 35294492
doi: 10.1371/journal.pone.0265418
pii: PONE-D-21-36274
pmc: PMC8926245
doi:
Substances chimiques
Bile Acids and Salts
0
Glycochenodeoxycholic Acid
640-79-9
Ursodeoxycholic Acid
724L30Y2QR
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0265418Subventions
Organisme : NIEHS NIH HHS
ID : P30 ES013508
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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