ArticleThe Journal of pathology2011
Hypoxia-inducible factor-1 signalling promotes goblet cell hyperplasia in airway epithelium.
Article in The Journal of pathology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 3 of them syntheses that pooled it.
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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
48 citing papers in PubMed, 3 syntheses or guidelines pooled it, 72 citations in OpenAlex.
- Cross-species systems analysis distinguishes inflammatory remodeling from primary mucus secretory failure in inflammatory bowel disease.Frontiers in immunology · 2026Pooled it
- Smoking and vaping alter genes related to mechanisms of SARS-CoV-2 susceptibility and severity: a systematic review and meta-analysis.The European respiratory journal · 2024Pooled it
- Current strategies and opportunities to manufacture cells for modeling human lungs.Advanced drug delivery reviews · 2020Pooled it
- Article
- Structural and cellular mechanisms of mucus plugging in the larger airways.Chinese medical journal pulmonary and critical care medicine · 2026Review
- Chronic Hypobaric Hypoxia at High Altitudes Aggravates Chronic Obstructive Pulmonary Disease in Mice.Journal of inflammation research · 2026Article
- Hypoxia: a critical pathophysiological driver in respiratory inflammatory diseases.Military Medical Research · 2026Review
- The role and mechanisms of the HIF-1 signaling pathway in LC-COPD.Journal of cancer research and clinical oncology · 2025Review
- Hypoxia promotes airway differentiation in the human lung epithelium.Cell stem cell · 2025Article
- Hyperconcentrated mucus in small airways: a mechanistic model for the pathogenesis of paediatric bronchiectasis.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- The oxygen level in air directs airway epithelial cell differentiation by controlling mitochondrial citrate export.Science advances · 2025Article
- Hypoxia-inducible factor 2 regulates alveolar regeneration after repetitive injury in three-dimensional cellular and in vivo models.Science translational medicine · 2025Article
- From metabolic alterations to chronic inflammation: mechanisms and immunoregulation of metabolic reprogramming in COPD.Frontiers in immunology · 2025Review
- Neutrophil elastase promotes mucin secretion in airway epithelial cells through the MARCKS/ACK1/cortactin pathway.Central-European journal of immunology · 2025Article
- Quantitative adverse outcome pathway modeling for cigarette smoke-inducible airway mucus hypersecretion. Part 2: Bayesian network modeling for probabilistic risk estimation.Frontiers in toxicology · 2025Article
- Role of Digoxin in Preventing Cigarette Smoke-Induced COPD via HIF-1α Inhibition in a Mouse Model.International journal of chronic obstructive pulmonary disease · 2025Article
- Influence of Hypoxia on the Airway Epithelium.Physiological research · 2024Review
- Airway epithelium damage in acute respiratory distress syndrome.Critical care (London, England) · 2024Article
- Review
- Dietary Beetroot Juice - Effects in Patients with COPD: A Review.International journal of chronic obstructive pulmonary disease · 2024Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Goblet cell hyperplasia is a common feature of chronic obstructive pulmonary disease (COPD) airways, but the mechanisms that underlie this epithelial remodelling in COPD are not understood. Based on our previous finding of hypoxia-inducible factor-1α (HIF-1α) nuclear localization in large airways from patients with COPD, we investigated whether hypoxia-inducible signalling could influence the development of goblet cell hyperplasia. We evaluated large airway samples obtained from 18 lifelong non-smokers and 13 former smokers without COPD, and 45 former smokers with COPD. In these specimens, HIF-1α nuclear staining occurred almost exclusively in COPD patients in areas of airway remodelling. In COPD patients, 93.2 ± 3.9% (range 65-100%) of goblet cells were HIF-1α positive in areas of goblet cell hyperplasia, whereas nuclear HIF-1α was not detected in individuals without COPD or in normal-appearing pseudostratified epithelium from COPD patients. To determine the direct effects of hypoxia-inducible signalling on epithelial cell differentiation in vitro, human bronchial epithelial cells (HBECs) were grown in air-liquid interface cultures under hypoxia (1% O(2)) or following treatment with a selective HIF-1α stabilizer, (2R)-[(4-biphenylylsulphonyl)amino]-N-hydroxy-3-phenyl-propionamide (BiPS). HBECs grown in hypoxia or with BiPS treatment were characterized by HIF-1α activation, carbonic anhydrase IX expression, mucus-producing cell hyperplasia and increased expression of MUC5AC. Analysis of signal transduction pathways in cells with HIF-1α activation showed increased ERK1/2 phosphorylation without activation of epidermal growth factor receptor, Ras, PI3K-Akt or STAT6. These data indicate an important effect of hypoxia-inducible signalling on airway epithelial cell differentiation and identify a new potential target to limit mucus production in COPD.
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Registered trials
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