ArticleCellular and molecular gastroenterology and hepatology2020
Novel Human NKCC1 Mutations Cause Defects in Goblet Cell Mucus Secretion and Chronic Inflammation.
Article in Cellular and molecular gastroenterology and hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Chasing the ghost in the code: highlighting the mystery of a rare genetic condition.American journal of physiology. Cell physiology · 2026Review
- Association Between Genetically Proxied SLC12A2 Inhibition and Inflammatory Bowel Disease: A Mendelian Randomization Study.Biochemical genetics · 2026Article
- Lactiplantibacillus plantarum ZJ316 Alleviates Helicobacter pylori-Induced Intestinal Inflammation by Sustaining Intestinal Homeostasis.Probiotics and antimicrobial proteins · 2025Article
- The effects of citral on the intestinal health and growth performance of American bullfrogs (Aquarana catesbeiana).BMC veterinary research · 2025Article
- Diuretics: a review of the pharmacology and effects on glucose homeostasis.Frontiers in pharmacology · 2025Review
- Association between Decreased SGK1 and Increased Intestinal α-Synuclein in an MPTP Mouse Model of Parkinson's Disease.International journal of molecular sciences · 2023Article
- NKCC1 in human diseases: is theAmerican journal of physiology. Cell physiology · 2023Article
- Loss of NKCC1 function increases epithelial tight junction permeability by upregulating claudin-2 expression.American journal of physiology. Cell physiology · 2022Article
- Clearance of small intestinal crypts involves goblet cell mucus secretion by intracellular granule rupture and enterocyte ion transport.Science signaling · 2022Article
- Confluence and tight junction dependence of volume regulation in epithelial tissue.Molecular biology of the cell · 2022Article
- Exosomal CagA from Helicobacter pylori aggravates intestinal epithelium barrier dysfunction in chronic colitis by facilitating Claudin-2 expression.Gut pathogens · 2022Article
- Review
- Cation-coupled chloride cotransporters: chemical insights and disease implications.Trends in chemistry · 2021Review
- Advances in the development of novel compounds targeting cation-chloride cotransporter physiology.American journal of physiology. Cell physiology · 2021Review
- Goblet cell LRRC26 regulates BK channel activation and protects against colitis in mice.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- NKCC1: Newly Found as a Human Disease-Causing Ion Transporter.Function (Oxford, England) · 2021Review
- A mutation in the Na-K-2Cl cotransporter-1 leads to changes in cellular metabolism.Journal of cellular physiology · 2020Article
- Sodium Transporters in Human Health and Disease.Frontiers in physiology · 2020Review
- Physiological Processes Modulated by the Chloride-Sensitive WNK-SPAK/OSR1 Kinase Signaling Pathway and the Cation-Coupled Chloride Cotransporters.Frontiers in physiology · 2020Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsInfections resulting from intestinal yeast and bacteria affect a large number of patients with deficits in absorptive or secretory epithelial transport mechanisms. The basolateral Na
methodsTo investigate how NKCC1 affects the integrity and function of the gut epithelia, we used a mouse model recapitulating the NKCC1-DFX patient mutation. Electron microscopy and immunostaining were used to analyze the integrity of the colonic mucus layers and immune cell infiltration. Fluorescence in situ hybridization was performed on the distal colon sections to measure bacteria translocation to the mucosa and submucosa. Citrobacter rodentium was used to measure mouse ability to clear enteric infection. A multiplex cytokine assay was used to analyze mouse inflammatory response to infection.
resultsWe show that NKCC1-DFX expression causes defective goblet cell mucus granule exocytosis, leading to secretion of intact granules into the lumen of the large intestine. In addition, NKCC1-DFX colon submucosal glands secrete mucus that remained attached to the epithelium. Importantly, expression of the mutant NKCC1 or complete loss of NKCC1 function leads to aggravated inflammatory response to C rodentium infection. Compared with wild-type, NKCC1-DFX mice showed decreased expression of claudin-2, a tight junction protein involved in paracellular Na
conclusionsOur data indicate that NKCC1-DFX impairs gut barrier function by affecting mucus secretion and immune properties.
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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.