ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2013
Chymase-mediated intestinal epithelial permeability is regulated by a protease-activating receptor/matrix metalloproteinase-2-dependent mechanism.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 76 citations in OpenAlex.
- A review on MMP-2 modulating agents from natural and synthetic sources and their role in inflammatory bowel disease.Inflammopharmacology · 2026Review
- Mast cell proteases and their significance in physiology, pathology, and therapeutic approaches.Pharmacological reviews · 2026Review
- Role of Bruton's Tyrosine Kinase in mast cell driven urothelial barrier injury in an LL-37 induced model of interstitial cystitis.Scientific reports · 2026Article
- The Gut Microbiota-Mast Cell Axis in Intestinal Homeostasis and Food Allergy Pathogenesis.Biomolecules · 2026Review
- Reviewing the Peripheral and Central Mechanisms of Visceral Hypersensitivity in Intestinal Disorders.International journal of medical sciences · 2026Review
- Food allergy: begin at the skin, end at the mast cell?Nature reviews. Immunology · 2025Review
- Role of Mast Cells in Eosinophilic Gastrointestinal Diseases.Immunology and allergy clinics of North America · 2024Review
- HOXD10 regulates intestinal permeability and inhibits inflammation of dextran sulfate sodium-induced ulcerative colitis through the inactivation of the Rho/ROCK/MMPs axis.Open medicine (Warsaw, Poland) · 2024Article
- Oral vancomycin treatment suppresses gut trypsin activity and preserves intestinal barrier function during EAE.iScience · 2023Article
- Optimal molecular binding data and pharmacokinetic profiles of novel potential triple-action inhibitors of chymase, spleen tyrosine kinase, and prostaglandin D2 receptor in the treatment of asthma.Journal, genetic engineering & biotechnology · 2023Article
- Increased Chymase-Positive Mast Cells in High-Grade Mucoepidermoid Carcinoma of the Parotid Gland.International journal of molecular sciences · 2023Article
- Pretreatment with propofol restores intestinal epithelial cells integrity disrupted by mast cell degranulation in vitro.Physiological research · 2022Article
- Mast cell mediation of visceral sensation and permeability in irritable bowel syndrome.Neurogastroenterology and motility · 2022Review
- Protease-activated receptor-2 activation enhances epithelial wound healing via epidermal growth factor receptor.Tissue barriers · 2022Article
- Mast Cell Proteases Tryptase and Chymase Induce Migratory and Morphological Alterations in Bronchial Epithelial Cells.International journal of molecular sciences · 2021Article
- Microbiota-Host Immunity Communication in Neurodegenerative Disorders: Bioengineering Challenges for In Vitro Modeling.Advanced healthcare materials · 2021Review
- Oral tolerance as antigen-specific immunotherapy.Immunotherapy advances · 2021Review
- Stem Cell Factor Neutralization Protects From Severe Anaphylaxis in a Murine Model of Food Allergy.Frontiers in immunology · 2021Article
- Dysregulation of intestinal epithelial CFTR-dependent ClMucosal immunology · 2021Article
- Mast Cell Chymase and Kidney Disease.International journal of molecular sciences · 2020Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Mast cells regulate intestinal barrier function during disease and homeostasis. Secretion of the mast cell-specific serine protease chymase regulates homeostasis. In the present study, we employ in vitro model systems to delineate the molecular pathways involved in chymase-mediated intestinal epithelial barrier dysfunction. Chymase stimulation of intestinal epithelial (Caco-2 BBe) cell monolayers induced a significant reduction in transepithelial resistance, indicating decreased intestinal epithelial barrier function. The chymase-induced intestinal epithelial barrier dysfunction was characterized by chymase-induced protease-activated receptor (PAR)-2 activation and matrix metalloproteinase (MMP)-2 expression and activation. Consistent with this observation, in vitro analysis revealed chymase-induced PAR-2 activation and increased MAPK activity and MMP-2 expression. Pharmacological and small interfering RNA-mediated antagonism of PAR-2 and MMP-2 significantly attenuated chymase-stimulated barrier dysfunction. Additionally, the chymase/MMP-2-mediated intestinal epithelial dysfunction was associated with a significant reduction in the tight junction protein claudin-5, which was partially restored by MMP-2 inhibition. Finally, incubation of Caco-2 BBe cells with chymase-sufficient, but not chymase-deficient, bone marrow-derived mast cells decreased barrier function, which was attenuated by the chymase inhibitor chymostatin. Collectively, these results suggest that mast cell/chymase-mediated intestinal epithelial barrier function is mediated by PAR-2/MMP-2-dependent pathways.
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