Early intrahepatic duct defects in a cystic fibrosis porcine model

Keyan Zarei; David K Meyerholz; David A Stoltz

doi:10.14814/phy2.14978

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Early intrahepatic duct defects in a cystic fibrosis porcine model

Journal article

Open access

Peer reviewed

Early intrahepatic duct defects in a cystic fibrosis porcine model

Keyan Zarei, David K Meyerholz and David A Stoltz

Physiological reports, Vol.9(14), pp.e14978-n/a

07/2021

DOI: 10.14814/phy2.14978

PMCID: PMC8290831

PMID: 34288572

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Abstract

Hepatobiliary disease causes significant morbidity and mortality in people with cystic fibrosis (CF), yet this problem remains understudied. Previous studies in the newborn CF pig demonstrated decreased bile flow into the small intestine and a microgallbladder with increased luminal mucus and fluid secretion defects. In this study, we examined the intrahepatic bile ducts of the newborn CF pig. We assessed whether our findings from the gallbladder are present elsewhere in the porcine biliary tract and if CF pig cholangiocytes have fluid secretion defects. Immunohistochemistry demonstrated apical CFTR expression in non‐CF pig intrahepatic bile ducts of a variety of sizes; CF pig intrahepatic bile ducts lacked CFTR expression. Assessment of serum markers did not reveal significant signs of hepatobiliary disease except for an elevation in direct bilirubin. Quantitative histology demonstrated that CF pigs had smaller bile ducts that more frequently contained luminal mucus. CF intrahepatic cholangiocyte organoids were smaller and lacked cAMP‐mediated fluid secretion. Together these data suggest that cholangiocyte fluid secretion is decreased in the CF pig, contributing to structural changes in bile ducts and decreased biliary flow. Using a porcine CF model, we discovered that intrahepatic ducts in newborn CF pigs have structural changes and are commonly plugged with mucus. CF intrahepatic cholangiocyte organoids had impaired cAMP‐mediated fluid secretion. Together these data suggest that impaired cholangiocyte fluid secretion contributes to structural changes in bile ducts, bile duct plugging, and decreased biliary flow.

CFTR

cholangiocytes

cystic fibrosis

intrahepatic bile ducts

organoids

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Details

Title: Subtitle: Early intrahepatic duct defects in a cystic fibrosis porcine model
Creators: Keyan Zarei - Department of Internal Medicine Roy J. and Lucille A. Carver College of MedicineUniversity of Iowa Iowa City IA USA
David K Meyerholz - Department of Pathology Roy J. and Lucille A. Carver College of MedicineUniversity of Iowa Iowa City IA USA
David A Stoltz - Department of Internal Medicine Roy J. and Lucille A. Carver College of MedicineUniversity of Iowa Iowa City IA USA
Resource Type: Journal article
Publication Details: Physiological reports, Vol.9(14), pp.e14978-n/a
DOI: 10.14814/phy2.14978
PMID: 34288572
PMCID: PMC8290831
NLM abbreviation: Physiol Rep
eISSN: 2051-817X
Publisher: John Wiley and Sons Inc
Grant note: GM007337; HL007638; HL091842 / ; STOLTZ19R0 / ;
Alternative title: ZAREI et al
Language: English
Date published: 07/2021
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Pathology; Internal Medicine
Record Identifier: 9984186651602771

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