Apical bulkheads accumulate as adaptive response to impaired bile flow in liver disease.
Apical bulkheads
Bile canaliculi
Hepatocyte rosettes
Hepatocytes
Primary sclerosing cholangitis
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
06 09 2023
06 09 2023
Historique:
revised:
11
07
2023
received:
13
03
2023
accepted:
13
07
2023
medline:
7
9
2023
pubmed:
31
7
2023
entrez:
31
7
2023
Statut:
ppublish
Résumé
Hepatocytes form bile canaliculi that dynamically respond to the signalling activity of bile acids and bile flow. Little is known about their responses to intraluminal pressure. During embryonic development, hepatocytes assemble apical bulkheads that increase the canalicular resistance to intraluminal pressure. Here, we investigate whether they also protect bile canaliculi against elevated pressure upon impaired bile flow in adult liver. Apical bulkheads accumulate upon bile flow obstruction in mouse models and patients with primary sclerosing cholangitis (PSC). Their loss under these conditions leads to abnormally dilated canaliculi, resembling liver cell rosettes described in other hepatic diseases. 3D reconstruction reveals that these structures are sections of cysts and tubes formed by hepatocytes. Mathematical modelling establishes that they positively correlate with canalicular pressure and occur in early PSC stages. Using primary hepatocytes and 3D organoids, we demonstrate that excessive canalicular pressure causes the loss of apical bulkheads and formation of rosettes. Our results suggest that apical bulkheads are a protective mechanism of hepatocytes against impaired bile flow, highlighting the role of canalicular pressure in liver diseases.
Identifiants
pubmed: 37522754
doi: 10.15252/embr.202357181
pmc: PMC10481669
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e57181Informations de copyright
© 2023 The Authors. Published under the terms of the CC BY 4.0 license.
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