ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2021
Dysregulated retinoic acid signaling in airway smooth muscle cells in asthma.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026Review
- Genetic background influences developmental airway smooth muscle program and susceptibility to airway hyperresponsiveness in mice.JCI insight · 2026Article
- Effect of Maternal Administration with All-Trans Retinoic Acid on Lungs of Neonatal Pigs.Veterinary sciences · 2025Article
- Genetic background and transient prenatal disruption of vitamin A signaling determine susceptibility to airway hyperresponsiveness in mice.bioRxiv : the preprint server for biology · 2025Article
- Eosinophil-derived interleukin-24 compromises epithelial integrity and aggravates airway remodeling in mouse models of allergic asthma.Nature communications · 2025Article
- Vitamin A and Its Related Diseases.Food science & nutrition · 2025Review
- The role of mesenchymal stem cell‑derived exosomes in asthma (Review).Molecular medicine reports · 2025Review
- A mode of action protein based approach that characterizes the relationships among most major diseases.Scientific reports · 2025Article
- Review
- Quantification of All-Trans Retinoic Acid and Cytokine Levels After Fungal, Viral and Bacterial Infections in the Lung.Journal of cellular and molecular medicine · 2025Article
- Retinoic Acid (RA): A Critical Immunoregulatory Molecule in Asthma and Allergies.Immunity, inflammation and disease · 2024Review
- Malnutrition and Allergies: Tipping the Immune Balance towards Health.Journal of clinical medicine · 2024Review
- Article
- Roles of Exosomal miRNAs in Asthma: Mechanisms and Applications.Journal of asthma and allergy · 2024Review
- Antioxidant Intake and Biomarkers of Asthma in Relation to Smoking Status-A Review.Current issues in molecular biology · 2023Review
- The Role of Vitamins in the Pathogenesis of Asthma.International journal of molecular sciences · 2023Review
- Article
- Review
- Retinoid metabolism: new insights.Journal of molecular endocrinology · 2022Review
- Molecular determinants of airway smooth muscle cells in health and disease.Annals of translational medicine · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Vitamin A deficiency has been shown to exacerbate allergic asthma. Previous studies have postulated that retinoic acid (RA), an active metabolite of vitamin A and high-affinity ligand for RA receptor (RAR), is reduced in airway inflammatory condition and contributes to multiple features of asthma including airway hyperresponsiveness and excessive accumulation of airway smooth muscle (ASM) cells. In this study, we directly quantified RA and examined the molecular basis for reduced RA levels and RA-mediated signaling in lungs and ASM cells obtained from asthmatic donors and in lungs from allergen-challenged mice. Levels of RA and retinol were significantly lower in lung tissues from asthmatic donors and house dust mite (HDM)-challenged mice compared to non-asthmatic human lungs and PBS-challenged mice, respectively. Quantification of mRNA and protein expression revealed dysregulation in the first step of RA biosynthesis consistent with reduced RA including decreased protein expression of retinol dehydrogenase (RDH)-10 and increased protein expression of RDH11 and dehydrogenase/reductase (DHRS)-4 in asthmatic lung. Proteomic profiling of non-asthmatic and asthmatic lungs also showed significant changes in the protein expression of AP-1 targets consistent with increased AP-1 activity. Further, basal RA levels and RA biosynthetic capabilities were decreased in asthmatic human ASM cells. Treatment of human ASM cells with all-trans RA (ATRA) or the RARγ-specific agonist (CD1530) resulted in the inhibition of mitogen-induced cell proliferation and AP-1-dependent transcription. These data suggest that RA metabolism is decreased in asthmatic lung and that enhancing RAR signaling using ATRA or RARγ agonists may mitigate airway remodeling associated with asthma.
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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.