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Anion Transport Across Human Gallbladder Organoids and Monolayers
Fluid and anion secretion are important functions of the biliary tract. It has been established that cAMP regulates Na(+) absorption through NHE3. However, mechanisms of gallbladder anion transport are less defined. We created organoids and organoid-derived monolayers from human gallbladder tissue t...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171199/ https://www.ncbi.nlm.nih.gov/pubmed/35685290 http://dx.doi.org/10.3389/fphys.2022.882525 |
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author | Zarei, Keyan Thornell, Ian M. Stoltz, David A. |
author_facet | Zarei, Keyan Thornell, Ian M. Stoltz, David A. |
author_sort | Zarei, Keyan |
collection | PubMed |
description | Fluid and anion secretion are important functions of the biliary tract. It has been established that cAMP regulates Na(+) absorption through NHE3. However, mechanisms of gallbladder anion transport are less defined. We created organoids and organoid-derived monolayers from human gallbladder tissue to measure organoid swelling and transepithelial electrophysiology. In our in vitro models, forskolin-stimulation caused organoid swelling and increased transepithelial anion transport. Full organoid swelling required Cl(−)while changes in short-circuit current were HCO(3) (−)-dependent. Organoids and monolayers from an individual homozygous for the cystic fibrosis-causing ΔF508 CFTR mutation had no apical expression of CFTR and minimal changes in transepithelial current and conductance with forskolin treatment. However, organoid swelling remained intact. Dilution potential studies revealed that forskolin treatment increased the paracellular permeability to anions relative to cations. These data suggest a novel paracellular contribution to forskolin-stimulated fluid transport across the gallbladder epithelium. |
format | Online Article Text |
id | pubmed-9171199 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91711992022-06-08 Anion Transport Across Human Gallbladder Organoids and Monolayers Zarei, Keyan Thornell, Ian M. Stoltz, David A. Front Physiol Physiology Fluid and anion secretion are important functions of the biliary tract. It has been established that cAMP regulates Na(+) absorption through NHE3. However, mechanisms of gallbladder anion transport are less defined. We created organoids and organoid-derived monolayers from human gallbladder tissue to measure organoid swelling and transepithelial electrophysiology. In our in vitro models, forskolin-stimulation caused organoid swelling and increased transepithelial anion transport. Full organoid swelling required Cl(−)while changes in short-circuit current were HCO(3) (−)-dependent. Organoids and monolayers from an individual homozygous for the cystic fibrosis-causing ΔF508 CFTR mutation had no apical expression of CFTR and minimal changes in transepithelial current and conductance with forskolin treatment. However, organoid swelling remained intact. Dilution potential studies revealed that forskolin treatment increased the paracellular permeability to anions relative to cations. These data suggest a novel paracellular contribution to forskolin-stimulated fluid transport across the gallbladder epithelium. Frontiers Media S.A. 2022-05-24 /pmc/articles/PMC9171199/ /pubmed/35685290 http://dx.doi.org/10.3389/fphys.2022.882525 Text en Copyright © 2022 Zarei, Thornell and Stoltz. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Zarei, Keyan Thornell, Ian M. Stoltz, David A. Anion Transport Across Human Gallbladder Organoids and Monolayers |
title | Anion Transport Across Human Gallbladder Organoids and Monolayers |
title_full | Anion Transport Across Human Gallbladder Organoids and Monolayers |
title_fullStr | Anion Transport Across Human Gallbladder Organoids and Monolayers |
title_full_unstemmed | Anion Transport Across Human Gallbladder Organoids and Monolayers |
title_short | Anion Transport Across Human Gallbladder Organoids and Monolayers |
title_sort | anion transport across human gallbladder organoids and monolayers |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171199/ https://www.ncbi.nlm.nih.gov/pubmed/35685290 http://dx.doi.org/10.3389/fphys.2022.882525 |
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