ArticleBiology open2012
The loss of Hoxa5 function promotes Notch-dependent goblet cell metaplasia in lung airways.
Article in Biology open, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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.
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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
38 citing papers in PubMed, 75 citations in OpenAlex.
- Epithelial cells in chronic obstructive pulmonary disease exacerbations: Targets for lung repair.Pharmacological reviews · 2026Review
- HOXA5-driven transcriptional program in lung development.Developmental biology · 2025Article
- Identification of bronchial epithelial genes associated with type 2 eosinophilic inflammation in asthma.The Journal of allergy and clinical immunology · 2025Article
- The next frontier in lung development and regeneration research: harnessing iPSC models to illuminate notch signaling pathways.Frontiers in cell and developmental biology · 2025Review
- Loss of Hoxa5 function affects Hox gene expression in different biological contexts.Scientific reports · 2024Article
- Upregulation of Notch Signaling and Cell-Differentiation Inhibitory Transcription Factors in Stable Chronic Obstructive Pulmonary Disease Patients.International journal of molecular sciences · 2024Article
- Furin as a therapeutic target in cystic fibrosis airways disease.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- Pulmonary endogenous progenitor stem cell subpopulation: Physiology, pathogenesis, and progress.Journal of intensive medicine · 2023Review
- The emerging role of NOTCH3 receptor signalling in human lung diseases.Expert reviews in molecular medicine · 2022Review
- Bioinformatics Approach Predicts Candidate Targets for SARS-CoV-2 Infections to COPD Patients.BioMed research international · 2022Article
- The NOTCH3 Downstream Target HEYL Is Required for Efficient Human Airway Basal Cell Differentiation.Cells · 2021Article
- Cigarette Smoke Activates NOTCH3 to Promote Goblet Cell Differentiation in Human Airway Epithelial Cells.American journal of respiratory cell and molecular biology · 2021Article
- Deletion ofDisease models & mechanisms · 2020Article
- Article
- Canonical WNT pathway is activated in the airway epithelium in chronic obstructive pulmonary disease.EBioMedicine · 2020Article
- Notch Transduction in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2020Review
- Genome-wide DNA methylation profiling identifies epigenetic signatures of gastric cardiac intestinal metaplasia.Journal of translational medicine · 2020Article
- Notch signaling in the mammalian respiratory system, specifically the trachea and lungs, in development, homeostasis, regeneration, and disease.Development, growth & differentiation · 2020Review
- More Than Just a Barrier: The Immune Functions of the Airway Epithelium in Asthma Pathogenesis.Frontiers in immunology · 2020Review
- Consecutive Hypoxia Decreases Expression ofFrontiers in cell and developmental biology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hox genes encode transcription factors controlling complex developmental processes in various organs. Little is known, however, about how HOX proteins control cell fate. Herein, we demonstrate that the goblet cell metaplasia observed in lung airways from Hoxa5(-/-) mice originates from the transdifferentiation of Clara cells. Reduced CC10 expression in Hoxa5(-/-) embryos indicates that altered cell specification occurs prior to birth. The loss of Hoxa5 function does not preclude airway repair after naphthalene exposure, but the regenerated epithelium presents goblet cell metaplasia and less CC10-positive cells, demonstrating the essential role of Hoxa5 for correct differentiation. Goblet cell metaplasia in Hoxa5(-/-) mice is a FOXA2-independent process. However, it is associated with increased Notch signaling activity. Consistent with these findings, expression levels of activated NOTCH1 and the effector gene HEY2 are enhanced in patients with chronic obstructive pulmonary disease. In vivo administration of a γ-secretase inhibitor attenuates goblet cell metaplasia in Hoxa5(-/-) mice, highlighting the contribution of Notch signaling to the phenotype and suggesting a potential therapeutic strategy to inhibit goblet cell differentiation and mucus overproduction in airway diseases. In summary, the loss of Hoxa5 function in lung mesenchyme impacts on epithelial cell fate by modulating Notch signaling.
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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.