ArticleScience advances2023
Secretomics reveals gelatinase substrates at the blood-brain barrier that are implicated in astroglial barrier function.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- Systems Biology and Experimental Validation Enable Discovery of MMP9-Centered Networks, Anticancer Activity, and Pharmacodynamic Signature in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2026Article
- Biochemical signals from the extracellular matrix in inflammation and tumour immunology.Nature reviews. Immunology · 2026Review
- β-Dystroglycan Downregulation and Astrocytic Alterations: A Possible Role in Blood-Brain Barrier Disruption During Experimental Cerebral Malaria.Molecular neurobiology · 2025Article
- MMP-2/9 inhibition modulates sharp wave abundance, inhibitory proteoglycan sulfation, and fear memory in juvenile zebrafish: relevance to affective disorders.Molecular psychiatry · 2025Article
- Macrophage invasion into the Drosophila brain requires JAK/STAT-dependent MMP activation in the blood-brain barrier.PLoS biology · 2025Article
- MMP-9 affects dural cell composition and granulocyte accumulation during neuroinflammation.Frontiers in immunology · 2025Article
- Elevated plasma matrix metalloproteinase 9 in schizophrenia patients associated with poor antipsychotic treatment response and white matter density deficits.Schizophrenia (Heidelberg, Germany) · 2024Article
- Current state of neuroprotective therapy using antibiotics in human traumatic brain injury and animal models.BMC neuroscience · 2024Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The gelatinases, matrix metalloproteinase 2 (MMP-2) and MMP-9, are key for leukocyte penetration of the brain parenchymal border in neuroinflammation and the functional integrity of this barrier; however, it is unclear which MMP substrates are involved. Using a tailored, sensitive, label-free mass spectrometry-based secretome approach, not previously applied to nonimmune cells, we identified 119 MMP-9 and 21 MMP-2 potential substrates at the cell surface of primary astrocytes, including known substrates (β-dystroglycan) and a broad spectrum of previously unknown MMP-dependent events involved in cell-cell and cell-matrix interactions. Using neuroinflammation as a model of assessing compromised astroglial barrier function, a selection of the potential MMP substrates were confirmed in vivo and verified in human samples, including vascular cell adhesion molecule-1 and neuronal cell adhesion molecule. We provide a unique resource of potential MMP-2/MMP-9 substrates specific for the astroglia barrier. Our data support a role for the gelatinases in the formation and maintenance of this barrier but also in astrocyte-neuron interactions.
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Registered trials
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