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 models, forskolin-stimulation caused organoid swelling and increased transepithelial anion transport. Full organoid swelling required Clwhile changes in short-circuit current were HCO -dependent. Organoids and monolayers from an individual homozygous for the cystic fibrosis-causing 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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171199 | PMC |
| http://dx.doi.org/10.3389/fphys.2022.882525 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
EMC3 is critical for CFTR function and calcium mobilization in the mouse intestinal epithelium.
Am J Physiol Gastrointest Liver Physiol
December 2024
Division of Pediatric Pulmonology, Allergy, and Sleep Medicine, Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA 46202.
Article Synopsis
- Membrane proteins, particularly CFTR, are essential for gastrointestinal health, while the endoplasmic reticulum membrane protein complex (EMC) is crucial for inserting these proteins into cell membranes during synthesis.
- In mice with a deleted EMC subunit (EMC3ΔIEC), researchers found smaller size and altered intestinal structures, with fewer important cell types like goblet and Paneth cells.
- The study revealed that EMC is vital for the proper functioning of membrane proteins and maintaining calcium levels in intestinal epithelial cells, suggesting its importance in overall cellular functions.
A W1282X cystic fibrosis mouse allows the study of pharmacological and gene-editing therapeutics to restore CFTR function.
J Cyst Fibros
November 2024
Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, Ohio, United States. Electronic address:
Background: People with cystic fibrosis carrying two nonsense alleles lack CFTR-specific treatment. Growing evidence supports the hypothesis that nonsense mutation identity affects therapeutic response, calling for mutation-specific CF models. We describe a novel W1282X mouse model and compare it to an existing G542X mouse.
View Article and Find Full Text PDFElexacaftor/tezacaftor/ivacaftor efficacy in intestinal organoids with rare CFTR variants in comparison to CFTR-F508del and CFTR-wild type controls.
J Cyst Fibros
November 2024
Pneumology and Cystic Fibrosis Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Rome, Italy. Electronic address:
Cystic fibrosis is a life-shortening genetic disease caused by pathological variants of the cystic fibrosis transmembrane conductance regulator gene. The CFTR modulator therapy elexacaftor, tezacaftor and ivacaftor (ETI) rescues CFTR protein function and has made a significant impact on the lives of many people with CF. In Europe, ETI is currently available for people with CF who have at least one F508del mutation whilst the effect of ETI on rare CFTR variants remains unknown, albeit that many of such variants may be restored through ETI.
View Article and Find Full Text PDFThe e-Flower: A hydrogel-actuated 3D MEA for brain spheroid electrophysiology.
Sci Adv
October 2024
Laboratory for Soft Bioelectronic Interfaces, Neuro-X Institute, École Polytechnique Fédérale de Lausanne (EPFL), Geneva, Switzerland.
Traditional microelectrode arrays (MEAs) are limited to measuring electrophysiological activity in two dimensions, failing to capture the complexity of three-dimensional (3D) tissues such as neural organoids and spheroids. Here, we introduce a flower-shaped MEA (e-Flower) that can envelop submillimeter brain spheroids following actuation by the sole addition of the cell culture medium. Inspired by soft microgrippers, its actuation mechanism leverages the swelling properties of a polyacrylic acid hydrogel grafted to a polyimide substrate hosting the electrical interconnects.
View Article and Find Full Text PDFGene expression profile of intestinal organoids from people with cystic fibrosis upon exposure to elexacaftor/tezacaftor/ivacaftor.
J Cyst Fibros
September 2024
Department of Medical Microbiology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czechia.
The forskolin-induced swelling assay (FIS) in patient-derived intestinal organoids (PDIOs), used to determine in vitro responsiveness to elexacaftor/tezacaftor/ivacaftor (ETI), showed variability in swelling among PDIOs obtained from people with CF (pwCF) carrying the same F508del/F508del CFTR genotype. We aimed to characterise the effect of ETI on the transcriptional activity of PDIOs-derived cells to understand the intracellular processes triggered by ETI and the differences in treatment response. Six high- and six low-responding PDIOs to ETI, derived from F508del/F508del pwCF, were incubated with or without ETI for 2 to 6 h.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!