ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2016
Cellular chloride and bicarbonate retention alters intracellular pH regulation in Cftr KO crypt epithelium.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
15 citing papers in PubMed, 32 citations in OpenAlex.
- The Role of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in Enamel Formation.Calcified tissue international · 2026Article
- Host transcriptomic analysis reveals a defective intracellular environment that limits SARS-CoV-2 replication in CFTR-deficient airway epithelium.Frontiers in cellular and infection microbiology · 2026Article
- Valproic Acid Promotes the Differentiation of Satellite Glial Cells into Neurons via the pH-Dependent Pathway.Biomolecules · 2025Article
- Human Colonoid-Myofibroblast Coculture for Study of Apical NaInternational journal of molecular sciences · 2023Article
- Gastric precancerous lesions:occurrence, development factors, and treatment.Frontiers in oncology · 2023Review
- SLC26A9 deficiency causes gastric intraepithelial neoplasia in mice and aggressive gastric cancer in humans.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- Carbonic anhydrase and soluble adenylate cyclase regulation of cystic fibrosis cellular phenotypes.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- The Role of pHFrontiers in cell and developmental biology · 2021Review
- The Effect of Sodium Bicarbonate, a Beneficial Adjuvant Molecule in Cystic Fibrosis, on Bronchial Epithelial Cells Expressing a Wild-Type or Mutant CFTR Channel.International journal of molecular sciences · 2020Article
- Cystic fibrosis transmembrane conductance regulator-emerging regulator of cancer.Cellular and molecular life sciences : CMLS · 2018Review
- Cftr Modulates Wnt/β-Catenin Signaling and Stem Cell Proliferation in Murine Intestine.Cellular and molecular gastroenterology and hepatology · 2018Article
- A primary human macrophage-enteroid co-culture model to investigate mucosal gut physiology and host-pathogen interactions.Scientific reports · 2017Article
- Intestinal Organoids: New Frontiers in the Study of Intestinal Disease and Physiology.Journal of pediatric gastroenterology and nutrition · 2017Review
- Human mini-guts: new insights into intestinal physiology and host-pathogen interactions.Nature reviews. Gastroenterology & hepatology · 2016Review
- The third dimension: new developments in cell culture models for colorectal research.Cellular and molecular life sciences : CMLS · 2016Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), an anion channel providing a major pathway for Cl(-) and HCO3 (-) efflux across the apical membrane of the epithelium. In the intestine, CF manifests as obstructive syndromes, dysbiosis, inflammation, and an increased risk for gastrointestinal cancer. Cftr knockout (KO) mice recapitulate CF intestinal disease, including intestinal hyperproliferation. Previous studies using Cftr KO intestinal organoids (enteroids) indicate that crypt epithelium maintains an alkaline intracellular pH (pHi). We hypothesized that Cftr has a cell-autonomous role in downregulating pHi that is incompletely compensated by acid-base regulation in its absence. Here, 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein microfluorimetry of enteroids showed that Cftr KO crypt epithelium sustains an alkaline pHi and resistance to cell acidification relative to wild-type. Quantitative real-time PCR revealed that Cftr KO enteroids exhibit downregulated transcription of base (HCO3 (-))-loading proteins and upregulation of the basolateral membrane HCO3 (-)-unloader anion exchanger 2 (Ae2). Although Cftr KO crypt epithelium had increased Ae2 expression and Ae2-mediated Cl(-)/HCO3 (-) exchange with maximized gradients, it also had increased intracellular Cl(-) concentration relative to wild-type. Pharmacological reduction of intracellular Cl(-) concentration in Cftr KO crypt epithelium normalized pHi, which was largely Ae2-dependent. We conclude that Cftr KO crypt epithelium maintains an alkaline pHi as a consequence of losing both Cl(-) and HCO3 (-) efflux, which impairs pHi regulation by Ae2. Retention of Cl(-) and an alkaline pHi in crypt epithelium may alter several cellular processes in the proliferative compartment of Cftr KO intestine.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.