ArticleJournal of cell science2011
MMP9 cleavage of the β4 integrin ectodomain leads to recurrent epithelial erosions in mice.
Article in Journal of cell science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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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.
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Who cites it
53 citing papers in PubMed, 76 citations in OpenAlex.
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- Matrix Metalloproteinases in Inflammatory Dermatoses.International journal of molecular sciences · 2025Review
- The function of metalloproteinases in pathophysiology of inflammatory bowel disease and colon cancer.Journal of leukocyte biology · 2025Review
- Shared Phenotypes of Immune Cells Recruited to the Cornea and the Surface of the Lens in Response to Formation of Corneal Erosions.The American journal of pathology · 2025Article
- Matrix Dynamics and Microbiome Crosstalk: Matrix Metalloproteinases as Key Players in Disease and Therapy.International journal of molecular sciences · 2025Review
- ROCK Inhibitor Enhances Neurite Outgrowth In Vitro and Corneal Sensory Nerve Reinnervation In Vivo.Investigative ophthalmology & visual science · 2024Article
- Single cell analysis of short-term dry eye induced changes in cornea immune cell populations.Frontiers in medicine · 2024Article
- Immune Cells Localize to Sites of Corneal Erosions in C57BL/6 Mice.Biomolecules · 2023Article
- Tumor-associated neutrophils in pancreatic cancer progression and metastasis.American journal of cancer research · 2023Review
- Article
- Activation of GRP78 ATPase suppresses A549 lung cancer cell migration by promoting ITGB4 degradation.Cell adhesion & migration · 2022Article
- Post-translational modifications to hemidesmosomes in human airway epithelial cells following diacetyl exposure.Scientific reports · 2022Article
- A Scoping Review of the Role of Metalloproteinases in the Pathogenesis of Autoimmune Pemphigus and Pemphigoid.Biomolecules · 2021Article
- SM1997 downregulates mustard-induced enzymes that disrupt corneal epithelial attachment.Anatomical record (Hoboken, N.J. : 2007) · 2021Article
- Alterations in corneal biomechanics underlie early stages of autoimmune-mediated dry eye disease.Journal of autoimmunity · 2020Article
- Integrin: Basement membrane adhesion by corneal epithelial and endothelial cells.Experimental eye research · 2020Review
- Biology of corneal fibrosis: soluble mediators, integrins, and extracellular vesicles.Eye (London, England) · 2020Article
- Neutrophils in the Tumor Microenvironment.Advances in experimental medicine and biology · 2020Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Integrin α6β4 is an integral membrane protein within hemidesmosomes and it mediates adhesion of epithelial cells to their underlying basement membrane. During wound healing, disassembly of hemidesmosomes must occur for sheet movement-mediated cell migration. The mechanisms of disassembly and reassembly of hemidesmosomes are not fully understood. The current study was initiated to understand the underlying cause of recurrent corneal erosions in the mouse. Here, we show that in vivo: (1) MMP9 levels are elevated and β4 integrin is partially cleaved in epithelial cell extracts derived from debridement wounded corneas; (2) the β4 ectodomain is missing from sites where erosions develop; and (3) β4 cleavage can be reduced by inhibiting MMP activity. Although β4, α3 and β1 integrins were all cleaved by several MMPs, only MMP9 was elevated in cell extracts derived from corneas with erosions. Coimmunoprecipitation studies showed that β4 integrin associates with MMP9, and protein clustering during immunoprecipitation induced proteolytic cleavage of the β4 integrin extracellular domain, generating a 100 kDa β4 integrin cytoplasmic domain fragment. Confocal imaging with three-dimensional reconstruction showed that MMP9 localizes at erosion sites in vivo where the ectodomain of β4 integrin is reduced or absent. MMP activation experiments using cultured corneal and epidermal keratinocytes showed reduced levels of α6β4 and β1 integrins within 20 minutes of phorbol ester treatment. This report is the first to show that β4 integrin associates with MMP9 and that its ectodomain is a target for cleavage by MMP9 in vivo under pathological conditions.
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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.