ArticleMucosal immunology2020
Exendin-4 restores airway mucus homeostasis through the GLP1R-PKA-PPARγ-FOXA2-phosphatase signaling.
Article in Mucosal immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 31 citations in OpenAlex.
- Immunometabolic Modulation in Obese Asthma: How GLP-1 Receptor Agonists Could Influence Systemic and Pulmonary Immune Phenotypes.Pulmonary therapy · 2026Review
- Pseudomonas aeruginosa-derived volatile organic compounds modulate AhR signaling to dysregulate airway mucus homeostasis.Nature communications · 2026Article
- Therapeutic Potential of Glucagon-like Peptide-1 Receptor Agonists in Respiratory Disorders.International journal of molecular sciences · 2026Review
- GLP-1RAs: antidiabetic drug crossover-new hope for chronic inflammatory airway diseases.Respiratory research · 2026Review
- Article
- Semaglutide and pioglitazone restore airway mucosal homeostasis by resolvingFrontiers in immunology · 2026Article
- Review
- Liraglutide upregulates the Cftr gene and regulates the mucus transcriptome profile in Brunner's glands in mice.Clinical and translational medicine · 2025Article
- GLP-1 receptor agonist protects glucose-stimulated insulin secretion in pancreatic β-cells against lipotoxicity via PPARδ/UCP2 pathway.Cellular and molecular life sciences : CMLS · 2025Article
- Association of GLP1RAs with risk of chronic obstructive pulmonary disease: evidence from drug target Mendelian randomization.Diabetology & metabolic syndrome · 2025Article
- Review
- Modulation of pulmonary immune functions by theFrontiers in immunology · 2025Review
- Potential Use of GLP-1 and GIP/GLP-1 Receptor Agonists for Respiratory Disorders: Where Are We at?Medicina (Kaunas, Lithuania) · 2024Review
- Ubiquitin-specific protease-7 promotes expression of airway mucin MUC5AC via the NF-κB signaling pathway.Heliyon · 2024Article
- Lung proteome and metabolome endotype in HIV-associated obstructive lung disease.ERJ open research · 2023Article
- The Role of Glucagon-Like Peptide-1 Receptor Agonists in Chronic Obstructive Pulmonary Disease.International journal of chronic obstructive pulmonary disease · 2023Review
- Glucagon-like peptide-1: a multi-faceted anti-inflammatory agent.Frontiers in immunology · 2023Review
- The anti-inflammatory feature of glucagon-like peptide-1 and its based diabetes drugs-Therapeutic potential exploration in lung injury.Acta pharmaceutica Sinica. B · 2022Review
- Tackling recalcitrant Pseudomonas aeruginosa infections in critical illness via anti-virulence monotherapy.Nature communications · 2022Article
- PTEN: An Emerging Potential Target for Therapeutic Intervention in Respiratory Diseases.Oxidative medicine and cellular longevity · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Goblet cell hyperplasia and metaplasia and excessive mucus are prominent pathologies of chronic airway diseases such as chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and chronic bronchitis. Chronic infection by respiratory pathogens, including Pseudomonas aeruginosa, exacerbates cyclical proinflammatory responses and mucus hypersecretion. P. aeruginosa and its virulence factor pyocyanin contribute to these pathologies by inhibiting FOXA2, a key transcriptional regulator of mucus homeostasis, through activation of antagonistic signaling pathways EGFR-AKT/ERK1/2 and IL-4/IL-13-STAT6-SPDEF. However, FOXA2-targeted therapy has not been previously explored. Here, we examined the feasibility of repurposing the incretin mimetic Exendin-4 to restore FOXA2-mediated airway mucus homeostasis. We have found that Exendin-4 restored FOXA2 expression, attenuated mucin production in COPD and CF-diseased airway cells, and reduced mucin and P. aeruginosa burden in mouse lungs. Mechanistically, Exendin-4 activated the GLP1R-PKA-PPAR-γ-dependent phosphatases PTEN and PTP1B, which inhibited key kinases within both EGFR and STAT6 signaling cascades. Our results may lead to the repurposing of Exendin-4 and other incretin mimetics to restore FOXA2 function and ultimately regulate excessive mucus in diseased airways.
Indexed as
Identifiers
What OpenQuestion holds
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.