Digitized pharmacokinetics data (Jeppesen1996)

Data digitized from publication.

Jeppesen1996 Description

Submitter: Matthias König

Assay type: Experimental Assay Type

Technology type: Technology Type

Investigation: Caffeine investigation

Study: PKDB Caffeine Study

Digitized pharmacokinetics data (Magnusson2008)

Data digitized from publication.

Magnusson2008 Description

Submitter: Matthias König

Assay type: Experimental Assay Type

Technology type: Technology Type

Investigation: Caffeine investigation

Study: PKDB Caffeine Study

Digitized pharmacokinetics data (Kaplan1997)

Data digitized from publication.

Kaplan1997 Description

Submitter: Matthias König

Assay type: Experimental Assay Type

Technology type: Technology Type

Investigation: Caffeine investigation

Study: PKDB Caffeine Study

Digitized pharmacokinetics data (Tanaka2014)

Data digitized from publication.

Tanaka2014 Description

Submitter: Matthias König

Assay type: Experimental Assay Type

Technology type: Technology Type

Investigation: Caffeine investigation

Study: PKDB Caffeine Study

Digitized pharmacokinetics data (Blanchard1983a)

Data digitized from publication.

Blanchard1983a Description

Submitter: Matthias König

Assay type: Experimental Assay Type

Technology type: Technology Type

Investigation: Caffeine investigation

Study: PKDB Caffeine Study

Digitized pharmacokinetics data (Healy1991)

Data digitized from publication.

Healy1991 Description

Submitter: Matthias König

Assay type: Experimental Assay Type

Technology type: Technology Type

Investigation: Caffeine investigation

Study: PKDB Caffeine Study

Digitized pharmacokinetics data (Haller2002)

Data digitized from publication.

Haller2002 Description

Submitter: Matthias König

Assay type: Experimental Assay Type

Technology type: Technology Type

Investigation: Caffeine investigation

Study: PKDB Caffeine Study

Digitized pharmacokinetics data (Kakuda2014)

Data digitized from publication.

Kakuda2014 Description

Submitter: Matthias König

Assay type: Experimental Assay Type

Technology type: Technology Type

Investigation: Caffeine investigation

Study: PKDB Caffeine Study

Digitized pharmacokinetics data (Oh2012)

Data digitized from publication.

Oh2012 Description

Submitter: Matthias König

Assay type: Experimental Assay Type

Technology type: Technology Type

Investigation: Caffeine investigation

Study: PKDB Caffeine Study

Digitized pharmacokinetics data (Amchin1999)

Data digitized from publication.

Amchin1999 Description

Submitter: Matthias König

Assay type: Experimental Assay Type

Technology type: Technology Type

Investigation: Caffeine investigation

Study: PKDB Caffeine Study

Digitized pharmacokinetics data (Perera2011)

Data digitized from publication.

Perera2011 Description

Submitter: Matthias König

Assay type: Experimental Assay Type

Technology type: Technology Type

Investigation: Caffeine investigation

Study: PKDB Caffeine Study

Digitized pharmacokinetics data (Akinyinka2000)

Data digitized from publication.

Akinyinka2000 Description

Submitter: Matthias König

Assay type: Experimental Assay Type

Technology type: Technology Type

Investigation: Caffeine investigation

Study: PKDB Caffeine Study

Digitized pharmacokinetics data (Spigset1999a)

Data digitized from publication.

Spigset1999a Description

Submitter: Matthias König

Assay type: Experimental Assay Type

Technology type: Technology Type

Investigation: Caffeine investigation

Study: PKDB Caffeine Study

Digitized pharmacokinetics data (Hetzler1990)

Data digitized from publication.

Hetzler1990 Description

Submitter: Matthias König

Assay type: Experimental Assay Type

Technology type: Technology Type

Investigation: Caffeine investigation

Study: PKDB Caffeine Study

Apical bulkheads accumulate as adaptive response to impaired bile flow in liver disease.

Abstract (Expand)

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.

Authors: C. Mayer, S. Nehring, M. Kucken, U. Repnik, S. Seifert, A. Sljukic, J. Delpierre, H. Morales-Navarrete, S. Hinz, M. Brosch, B. Chung, T. Karlsen, M. Huch, Y. Kalaidzidis, L. Brusch, J. Hampe, C. Schafmayer, M. Zerial

Date Published: 31st Jul 2023

Publication Type: Journal

Human microdissected liver tissue sample (GEO)

Human microdissected liver tissue sample

Published sample ID (String) *, Lab sample ID (String) *, Tissue (Controlled Vocabulary - Liver cell types) *, Organism (NCBI ID) , Sample web link (Web link) , Link to SOP used (Web link) , hepatic zone (Controlled Vocabulary - Hepatic zones in human hepatocytes) , Sample creation date (Date) , Molecule type (String)

liver, hepatocite, Human

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