ArticleEBioMedicine2018
Retinoic acid signaling balances adult distal lung epithelial progenitor cell growth and differentiation.
Article in EBioMedicine, 2018. 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, 78 citations in OpenAlex.
- Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026Review
- Inhaled vitamin A mitigates hyperoxia-induced acute and chronic lung damage in a neonatal rat model of bronchopulmonary dysplasia.American journal of respiratory cell and molecular biology · 2026Article
- Activation of ERBB4 Pathway Inhibits Pathological Transdifferentiation of Lung Epithelial Progenitors into CD66cAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Alveolar type 2 cell LRP1 is needed for surfactant phospholipid metabolism and pulmonary function in mice.Journal of lipid research · 2026Article
- Regenerative therapeutics for chronic obstructive pulmonary disease.Pharmacological reviews · 2026Review
- Epithelial remodeling and microbial dysbiosis in the lower respiratory tract of vitamin A-deficient mouse lungs.Scientific reports · 2026Article
- The Hypoxia-Retinoid Axis in Idiopathic Pulmonary Fibrosis: Multifaceted Etiology and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Isolation of Lung Retinoid-Containing Cells by Cell Sorting.Journal of visualized experiments : JoVE · 2025Article
- Lung organoids in COPD: recent advances and future prospects.Respiratory research · 2025Review
- Malnutrition and Allergies: Tipping the Immune Balance towards Health.Journal of clinical medicine · 2024Review
- Nephron progenitors rhythmically alternate between renewal and differentiation phases that synchronize with kidney branching morphogenesis.bioRxiv : the preprint server for biology · 2024Article
- Innovative three-dimensional models for understanding mechanisms underlying lung diseases: powerful tools for translational research.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- Article
- Inhibition of YAP1 activity ameliorates acute lung injury through promotion of M2 macrophage polarization.MedComm · 2023Article
- Optimization of Primary Human Bronchial Epithelial 3D Cell Culture with Donor-Matched Fibroblasts and Comparison of Two Different Culture Media.International journal of molecular sciences · 2023Article
- Retinoids stored locally in the lung are required to attenuate the severity of acute lung injury in male mice.Nature communications · 2023Article
- Pulmonary endogenous progenitor stem cell subpopulation: Physiology, pathogenesis, and progress.Journal of intensive medicine · 2023Review
- Mucus Hypersecretion in Chronic Obstructive Pulmonary Disease and Its Treatment.Mediators of inflammation · 2023Review
- Exploiting the potential of lung stem cells to develop pro-regenerative therapies.Biology open · 2022Review
- Lung Organoids in Smoking Research: Current Advances and Future Promises.Biomolecules · 2022Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDespite compelling data describing pro-regenerative effects of all-trans retinoic acid (ATRA) in pre-clinical models of chronic obstructive pulmonary disease (COPD), clinical trials using retinoids for emphysema patients have failed. Crucial information about the specific role of RA signaling in adult rodent and human lung epithelial progenitor cells is largely missing.
methodsAdult lung organoid cultures were generated from isolated primary mouse and human lung epithelial cells, and incubated with pharmacological pathway modulators and recombinant proteins. Organoid number and size were measured, and differentiation was assessed with quantitative immunofluorescence and gene expression analyses.
findingsWe unexpectedly found that ATRA decreased lung organoid size, whereas RA pathway inhibition increased mouse and human lung organoid size. RA pathway inhibition stimulated mouse lung epithelial proliferation via YAP pathway activation and epithelial-mesenchymal FGF signaling, while concomitantly suppressing alveolar and airway differentiation. HDAC inhibition rescued differentiation in growth-augmented lung organoids.
interpretationIn contrast to prevailing notions, our study suggests that regenerative pharmacology using transient RA pathway inhibition followed by HDAC inhibition might hold promise to promote lung epithelial regeneration in diseased adult lung tissue. FUND: This project is funded by the Lung Foundation Netherlands (Longfonds) grant 6.1.14.009 (RG, MK, JS, PSH) and W2/W3 Professorship Award by the Helmholtz Association, Berlin, Germany (MK).
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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.