ArticleAmerican journal of physiology. Lung cellular and molecular physiology2013
Zonulin as prehaptoglobin2 regulates lung permeability and activates the complement system.
Article in American journal of physiology. Lung cellular and molecular physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 67 citations in OpenAlex.
- Positive regulatory effects of perioperative probiotic treatment on postoperative liver complications after colorectal liver metastases surgery: a double-center and double-blind randomized clinical trial.BMC gastroenterology · 2015Trial
- Increased Intestinal Permeability and Articular Involvement in Systemic Lupus Erythematosus Patients-A Mutually Exclusive Relationship?Current issues in molecular biology · 2025Article
- Evaluation of Intestinal Permeability in Children Diagnosed With Bronchiolitis in Pediatric Emergency Department: A Cross-Sectional Study.Pediatric pulmonology · 2025Article
- Elucidating the Significance of Zonulin in the Pathogenesis of Chronic Inflammatory Disorders: Emphasis on Intestinal Barrier Function and Tight Junction Regulation.Current medicinal chemistry · 2025Review
- Mechanisms of Lung and Intestinal Microbiota and Innate Immune Changes Caused by Pathogenic Enterococcus Faecalis Promoting the Development of Pediatric Pneumonia.Microorganisms · 2023Article
- Could Zonulin and Presepsin Be Biomarkers and Therapeutic Targets for Acute Myocarditis?Arquivos brasileiros de cardiologia · 2023Article
- Serum Zonulin Is a Biomarker for Severe Asthma.Allergy, asthma & immunology research · 2023Article
- Zonulin as a Potential Therapeutic Target in Microbiota-Gut-Brain Axis Disorders: Encouraging Results and Emerging Questions.International journal of molecular sciences · 2023Review
- Circulating Microbial Cell-Free DNA in Health and Disease.International journal of molecular sciences · 2023Review
- Human coagulation factor X and CD5 antigen-like are potential new members of the zonulin family proteins.Biochemical and biophysical research communications · 2023Article
- Complement as a vital nexus of the pathobiological connectome for acute respiratory distress syndrome: An emerging therapeutic target.Frontiers in immunology · 2023Review
- Zonulin, as a marker of intestinal permeability, is elevated in IgA nephropathy and IgA vasculitis with nephritis.Clinical kidney journal · 2023Article
- Article
- Zonulin, a marker of gut permeability, is associated with mortality in a cohort of hospitalised peruvian COVID-19 patients.Frontiers in cellular and infection microbiology · 2022Article
- Loss of Gut Barrier Integrity In Lupus.Frontiers in immunology · 2022Review
- Molecular Dambusters: What Is Behind Hyperpermeability in Bradykinin-Mediated Angioedema?Clinical reviews in allergy & immunology · 2021Review
- Bacterial DNAemia is associated with serum zonulin levels in older subjects.Scientific reports · 2021Article
- Hemorrhagic shock induces renal complement activation.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2021Article
- Metformin effects on zonulin level in polycystic ovarian women.ADMET & DMPK · 2021Article
- Neurological Symptoms of COVID-19: The Zonulin Hypothesis.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Zonulin is a protein involved in the regulation of tight junctions (TJ) in epithelial or endothelial cells. Zonulin is known to affect TJ in gut epithelial cells, but little is known about its influences in other organs. Prehaptoglobin2 has been identified as zonulin and is related to serine proteases (MASPs, C1qrs) that activate the complement system. The current study focused on the role of zonulin in development of acute lung injury (ALI) in C57BL/6 male mice following intrapulmonary deposition of IgG immune complexes. A zonulin antagonist (AT-1001) and a related peptide with permeability agonist activities (AT-1002) were employed and given intratracheally or intravenously. Also, zonulin was blocked in lung with a neutralizing antibody. In a dose-dependent manner, AT-1001 or zonulin neutralizing antibody attenuated the intensity of ALI (as quantitated by albumin leak, neutrophil accumulation, and proinflammatory cytokines). A similar pattern was found using the bacterial lipopolysaccharide model of ALI. Using confocal microscopy on sections of injured lungs, staining patterns for TJ proteins were discontinuous, reduced, and fragmented. As expected, the leak of blood products into the alveolar space confirmed the passage of 3 and 20 kDa dextran, and albumin. In contrast to AT-1001, application of the zonulin agonist AT-1002 intensified ALI. Zonulin both in vitro and in vivo induced generation of complement C3a and C5a. Collectively, these data suggest that zonulin facilitates development of ALI both by enhancing albumin leak and complement activation as well as increased buildup of neutrophils and cytokines during development of ALI.
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