ArticleJCI insight2018
Matrix metalloproteinase-9 deficiency protects mice from severe influenza A viral infection.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06676124 (Modulation of MMP-9/NGAL Ratio in Diabetic Patients With Early Renal Dysfunction by Piper Crocatum Functional Foods), which is not on this map. Cited by 40 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Modulation of MMP-9/NGAL Ratio in Diabetic Patients With Early Renal Dysfunction by Piper Crocatum Functional Foods
Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Matrix metallopeptidase 9 as a host protein target of chloroquine and melatonin for immunoregulation in COVID-19: A network-based meta-analysis.Life sciences · 2020Pooled it
- Matrix Metalloproteinase-8 Deficiency Alters the Balance Between Viral Clearance and Immunopathology in H1N1 Infection.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Evaluation of antiviral activity indicators in selected medicinal plants used traditionally for treatment of respiratory viral infections.BMC complementary medicine and therapies · 2026Article
- Article
- Amplified inflammatory and immune responses in viral-associated pulmonary aspergillosis.Frontiers in cellular and infection microbiology · 2026Article
- Redox-Dependent Activation of Matrix Metalloproteinases Regulates Influenza A Virus Replication in Neuronal Cells.International journal of microbiology · 2026Article
- Activated Interferon-γ-Positive T Lymphocytes and Cytokine Signatures in Patients With Postinfectious Cough.MedComm · 2025Article
- Cyclosporin A alleviates influenza A (H1N1) virus-induced chronic pulmonary inflammation through decreasing IFN-γ-producing T lymphocytes.Virology journal · 2025Article
- Thioredoxin regulates T cell proliferation and aggravates the severity of influenza a virus infection.Scientific reports · 2025Article
- ZBP1-driven cell death in severe influenza.Trends in microbiology · 2025Review
- Galectin-3 disrupts tight junctions of airway epithelial cell monolayers by inducing expression and release of matrix metalloproteinases upon influenza A infection.Glycobiology · 2025Article
- PDGFRα-positive cell-derived TIMP-1 modulates adaptive immune responses to influenza A viral infection.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Post-influenza bacterial infection: mechanisms of pathogenesis and advances in therapeutic strategies.Frontiers in microbiology · 2025Review
- Estrogen-dependent gene regulation: Molecular basis of TIMP-1 as a sex-specific biomarker for acute lung injury.Physiological reports · 2024Article
- Article
- Club Cell Secretory Protein-16 (CC16) as a Prognostic Biomarker for COVID-19 and H1N1 Viral Infections.Diagnostics (Basel, Switzerland) · 2024Article
- Building a human lung from pluripotent stem cells to model respiratory viral infections.Respiratory research · 2024Review
- Host Cell Proteases Involved in Human Respiratory Viral Infections and Their Inhibitors: A Review.Viruses · 2024Review
- Proteolytic Vesicles Derived fromBiomedicines · 2024Article
- Phillyrin ameliorates influenza a virus-induced pulmonary inflammation by antagonizing CXCR2 and inhibiting NLRP3 inflammasome activation.Virology journal · 2023Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Matrix metalloproteinase-9 (MMP-9) cleaves various proteins to regulate inflammatory and injury responses. However, MMP-9's activities during influenza A viral (IAV) infections are incompletely understood. Herein, plasma MMP-9 levels were increased in patients with pandemic H1N1 and seasonal IAV infections. MMP-9 lung levels were increased and localized to airway epithelial cells and leukocytes in H1N1-infected WT murine lungs. H1N1-infected Mmp-9-/- mice had lower mortality rates, reduced weight loss, lower lung viral titers, and reduced lung injury, along with lower E-cadherin shedding in bronchoalveolar lavage fluid (BALF) samples than WT mice. H1N1-infected Mmp-9-/- mice had an altered immune response to IAV with lower BALF PMN and macrophage counts, higher Th1-like CD4+ and CD8+ T cell subsets, lower T regulatory cell counts, reduced lung type I interferon levels, and higher lung interferon-γ levels. Mmp-9 bone marrow-chimera studies revealed that Mmp-9 deficiency in lung parenchymal cells protected mice from IAV-induced mortality. H1N1-infected Mmp-9-/- lung epithelial cells had lower viral titers than H1N1-infected WT cells in vitro. Thus, H1N1-infected Mmp-9-/- mice are protected from IAV-induced lung disease due to a more effective adaptive immune response to IAV and reduced epithelial barrier injury due partly to reduced E-cadherin shedding. Thus, we believe that MMP-9 is a novel therapeutic target for IAV infections.
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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.