ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2009
Hypoxia inducible factor-1 (HIF-1)-mediated repression of cystic fibrosis transmembrane conductance regulator (CFTR) in the intestinal epithelium.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 84 citations in OpenAlex.
- Epigenetic regulation and chromatin organization in cystic fibrosis airways.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2026Review
- Structural and cellular mechanisms of mucus plugging in the larger airways.Chinese medical journal pulmonary and critical care medicine · 2026Review
- Cystic fibrosis airway epithelial cells have an exaggerated response to hypoxia that is partially reversible through transmembrane receptor modulation.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2025Article
- The advantages and challenges of sorafenib combination therapy: Drug resistance, toxicity and future directions (Review).Oncology letters · 2025Review
- The Role of Ion Channels in Pulmonary Hypertension: A Review.Pulmonary circulation · 2025Review
- Acquired dysfunction of CFTR underlies cystic fibrosis-like disease of the canine gallbladder.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Review
- Tissue-Specific Regulation ofInternational journal of molecular sciences · 2023Review
- Hypoxia represses FOXF1 in lung endothelial cells through HIF-1α.Frontiers in physiology · 2023Article
- Physiology and pathophysiology of human airway mucus.Physiological reviews · 2022Review
- The Hypoxia-Adenosine Link during Myocardial Ischemia-Reperfusion Injury.Biomedicines · 2022Review
- CFTR and Gastrointestinal Cancers: An Update.Journal of personalized medicine · 2022Review
- Intestinal secretory mechanisms and diarrhea.American journal of physiology. Gastrointestinal and liver physiology · 2022Review
- Review
- Hypoxia inhibits colonic uptake of the microbiota-generated forms of vitamin B1 via HIF-1α-mediated transcriptional regulation of their transporters.The Journal of biological chemistry · 2022Article
- Article
- Alternative adenosine Receptor activation: The netrin-Adora2b link.Frontiers in pharmacology · 2022Review
- Inferred inactivation of the Cftr gene in the duodena of mice exposed to hexavalent chromium (Cr(VI)) in drinking water supports its tumor-suppressor status and implies its potential role in Cr(VI)-induced carcinogenesis of the small intestines.Toxicology and applied pharmacology · 2021Article
- BACH1, the master regulator of oxidative stress, has a dual effect on CFTR expression.The Biochemical journal · 2021Article
- Transcriptomics Analysis Reveals the Immune Response Mechanism of Rabbits with Diarrhea Fed an Antibiotic-Free Diet.Animals : an open access journal from MDPI · 2021Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Diarrhea is widespread in intestinal diseases involving ischemia and/or hypoxia. Since hypoxia alters stimulated Cl(-) and water flux, we investigated the influence of such a physiologically and pathophysiologically important signal on expression of the cystic fibrosis transmembrane conductance regulator (CFTR). Located on the apical membrane, this cAMP-activated Cl(-) channel determines salt and fluid transport across mucosal surfaces. Our studies revealed depression of CFTR mRNA, protein, and function in hypoxic epithelia. Chromatin immunoprecipitation identified a previously unappreciated binding site for the hypoxia inducible factor-1 (HIF-1), and promoter studies established its relevance by loss of repression following point mutation. Consequently, HIF-1 overexpressing cells exhibited significantly reduced transport capacity in colorimetric Cl(-) efflux studies, altered short circuit measurements, and changes in transepithelial fluid movement. Whole-body hypoxia in wild-type mice resulted in significantly reduced small intestinal fluid and HCO(3)(-) secretory responses to forskolin. Experiments performed in Cftr(-/-) and Nkcc1(-/-) mice underlined the role of altered CFTR expression for these functional changes, and work in conditional Hif1a mutant mice verified HIF-1-dependent CFTR regulation in vivo. In summary, our study clarifies CFTR regulation and introduces the concept of a HIF-1-orchestrated response designed to regulate ion and fluid movement across hypoxic intestinal epithelia.
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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.