ArticleAmerican journal of respiratory cell and molecular biology2018
Role of Spdef in the Regulation of Muc5b Expression in the Airways of Naive and Mucoobstructed Mice.
Article in American journal of respiratory cell and molecular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
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- Modulation of pulmonary immune functions by theFrontiers in immunology · 2025Review
- Advanced Lung-on-a-Chip Technology: Mimicking the Complex Human Lung Microenvironment.International journal of biological sciences · 2025Article
- Transcriptional profiling of mucus production in rhesus macaque endocervical cells under hormonal regulation†.Biology of reproduction · 2024Article
- Biochemical and transcriptomic evaluation of a 3D lung organoid platform for pre-clinical testing of active substances targeting senescence.Respiratory research · 2024Article
- Genomic characterization and therapeutic utilization of IL-13-responsive sequences in asthma.Cell genomics · 2023Article
- A Splice Switch in SIGIRR Causes a Defect of IL-37-Dependent Anti-Inflammatory Activity in Cystic Fibrosis Airway Epithelial Cells.International journal of molecular sciences · 2022Article
- Differential gene expression of 3D primary human airway cultures exposed to cigarette smoke and electronic nicotine delivery system (ENDS) preparations.BMC medical genomics · 2022Article
- MUC5B regulates goblet cell differentiation and reduces inflammation in a murine COPD model.Respiratory research · 2022Article
- Regional Differences in Mucociliary Clearance in the Upper and Lower Airways.Frontiers in physiology · 2022Article
- The MUC5B-associated variant rs35705950 resides within an enhancer subject to lineage- and disease-dependent epigenetic remodeling.JCI insight · 2021Article
- Phenotypes of CF rabbits generated by CRISPR/Cas9-mediated disruption of the CFTR gene.JCI insight · 2021Article
- Efficient RNP-directed Human Gene Targeting Reveals SPDEF Is Required for IL-13-induced Mucostasis.American journal of respiratory cell and molecular biology · 2020Article
- Inactivation of FOXA2 by Respiratory Bacterial Pathogens and Dysregulation of Pulmonary Mucus Homeostasis.Frontiers in immunology · 2020Review
- WNT/RYK signaling restricts goblet cell differentiation during lung development and repair.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- IL-1β dominates the promucin secretory cytokine profile in cystic fibrosis.The Journal of clinical investigation · 2019Article
- Muc5b is mainly expressed and sialylated in the nasal olfactory epithelium whereas Muc5ac is exclusively expressed and fucosylated in the nasal respiratory epithelium.Histochemistry and cell biology · 2019Article
- XBP1S Regulates MUC5B in a Promoter Variant-Dependent Pathway in Idiopathic Pulmonary Fibrosis Airway Epithelia.American journal of respiratory and critical care medicine · 2019Article
- Immunopathology of Airway Surface Liquid Dehydration Disease.Journal of immunology research · 2019Review
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Understanding how expression of airway secretory mucins MUC5B and MUC5AC is regulated in health and disease is important to elucidating the pathogenesis of mucoobstructive respiratory diseases. The transcription factor SPDEF (sterile α-motif pointed domain epithelial specific transcription factor) is a key regulator of MUC5AC, but its role in regulating MUC5B in health and in mucoobstructive lung diseases is unknown. Characterization of Spdef-deficient mice upper and lower airways demonstrated region-specific, Spdef-dependent regulation of basal Muc5b expression. Neonatal Spdef-deficient mice exhibited reductions in BAL Muc5ac and Muc5b. Adult Spdef-deficient mice partially phenocopied Muc5b-deficient mice as they exhibited reduced Muc5b in nasopharyngeal and airway epithelia but not in olfactory Bowman glands, 75% incidence of nasopharyngeal hair/mucus plugs, and mild bacterial otitis media, without defective mucociliary clearance in the nasopharynx. In contrast, tracheal mucociliary clearance was reduced in Spdef-deficient mice in the absence of lung disease. To evaluate the role of Spdef in the development and persistence of Muc5b-predominant mucoobstructive lung disease, Spdef-deficient mice were crossed with Scnn1b-transgenic (Scnn1b-Tg) mice, which exhibit airway surface dehydration-induced airway mucus obstruction and inflammation. Spdef-deficient Scnn1b-Tg mice exhibited reduced Muc5ac, but not Muc5b, expression and BAL content. Airway mucus obstruction was not decreased in Spdef-deficient Scnn1b-Tg mice, consistent with Muc5b-dominant Scnn1b disease, but increased airway neutrophilia was observed compared with Spdef-sufficient Scnn1b-Tg mice. Collectively, these results indicate that Spdef regulates baseline Muc5b expression in respiratory epithelia but does not contribute to Muc5b regulation in a mouse model of Muc5b-predominant mucus obstruction caused by airway dehydration.
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