ArticleJCI insight2017
Guanylate cyclase 2C agonism corrects CFTR mutants.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed.
- Adoptive immune cell therapy for colorectal cancer.Frontiers in immunology · 2025Review
- DRA involvement in linaclotide-stimulated bicarbonate secretion during loss of CFTR function.JCI insight · 2024Article
- Key role of down-regulated in adenoma (bioRxiv : the preprint server for biology · 2024Article
- Functional Consequences of CFTR Interactions in Cystic Fibrosis.International journal of molecular sciences · 2024Review
- Microbiota-derived butyrate dampens linaclotide stimulation of the guanylate cyclase C pathway in patient-derived colonoids.Neurogastroenterology and motility · 2023Article
- Review
- Guanylate cyclase-C agonists as peripherally acting treatments of chronic visceral pain.Trends in pharmacological sciences · 2022Review
- Patient personalized translational tools in cystic fibrosis to transform data from bench to bed-side and back.American journal of physiology. Gastrointestinal and liver physiology · 2021Article
- Luminal Gastrointestinal Manifestations of Cystic Fibrosis.Current gastroenterology reports · 2021Review
- Synergy between Readthrough and Nonsense Mediated Decay Inhibition in a Murine Model of Cystic Fibrosis Nonsense Mutations.International journal of molecular sciences · 2020Article
- Targeting the Heme Oxygenase 1/Carbon Monoxide Pathway to Resolve Lung Hyper-Inflammation and Restore a Regulated Immune Response in Cystic Fibrosis.Frontiers in pharmacology · 2020Review
- Targeting DNAJB9, a novel ER luminal co-chaperone, to rescue ΔF508-CFTR.Scientific reports · 2019Article
- Carbocisteine stimulated an increase in ciliary bend angle via a decrease in [ClPflugers Archiv : European journal of physiology · 2019Article
- CFTR modulator theratyping: Current status, gaps and future directions.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2019Review
- Linaclotide improves gastrointestinal transit in cystic fibrosis mice by inhibiting sodium/hydrogen exchanger 3.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- AC6 is the major adenylate cyclase forming a diarrheagenic protein complex with cystic fibrosis transmembrane conductance regulator in cholera.The Journal of biological chemistry · 2018Article
- Personalized medicine in CF: from modulator development to therapy for cystic fibrosis patients with rare CFTR mutations.American journal of physiology. Lung cellular and molecular physiology · 2018Review
- Transepithelial Fluid and Salt Re-Absorption Regulated by cGK2 Signals.International journal of molecular sciences · 2018Review
- Guanylate cyclase C reduces invasion of intestinal epithelial cells by bacterial pathogens.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Cystic fibrosis (CF) is a genetic disorder in which epithelium-generated fluid flow from the lung, intestine, and pancreas is impaired due to mutations disrupting CF transmembrane conductance regulator (CFTR) channel function. CF manifestations of the pancreas and lung are present in the vast majority of CF patients, and 15% of CF infants are born with obstructed gut or meconium ileus. However, constipation is a significantly underreported outcome of CF disease, affecting 47% of the CF patients, and management becomes critical in the wake of increasing life span of CF patients. In this study, we unraveled a potentially novel molecular role of a membrane-bound cyclic guanosine monophosphate-synthesizing (cGMP-synthesizing) intestinal enzyme, guanylate cyclase 2C (GCC) that could be targeted to ameliorate CF-associated intestinal fluid deficit. We demonstrated that GCC agonism results in functional rescue of murine F508del/F508del and R117H/R117H Cftr and CFTR mutants in CF patient-derived intestinal spheres. GCC coexpression and activation facilitated processing and ER exit of F508del CFTR and presented a potentially novel rescue modality in the intestine, similar to the CF corrector VX-809. Our findings identify GCC as a biological CFTR corrector and potentiator in the 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.