ArticleGlia2018
MMP7 cleaves remyelination-impairing fibronectin aggregates and its expression is reduced in chronic multiple sclerosis lesions.
Article in Glia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- Extracellular matrix remodeling therapeutic strategies to tackle central nervous system diseases.Neural regeneration research · 2026Article
- Recombinant rat heat shock protein 70 (rrHSP70) may promote remyelination by regulating microglia/macrophages and oligodendrocytes in a toxin-induced demyelination animal model.Frontiers in immunology · 2026Article
- Article
- Oxymatrine possibly inhibits differentiation and maturation of oligodendrocytes in the remyelination of the toxin-induced demyelination animal model.Metabolic brain disease · 2025Article
- Making tracks: microglia and the extracellular matrix.Molecular neurodegeneration · 2025Review
- The Future of PET Imaging in Multiple Sclerosis: Characterisation of Individual White Matter Lesions.Journal of clinical medicine · 2025Review
- Article
- Astrocytic TIMP-1 regulates production of Anastellin, an inhibitor of oligodendrocyte differentiation and FTY720 responses.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The role of fibronectin in multiple sclerosis and the effect of drug delivery across the blood-brain barrier.Neural regeneration research · 2023Review
- Poly-L-ornithine blocks the inhibitory effects of fibronectin on oligodendrocyte differentiation and promotes myelin repair.Neural regeneration research · 2023Article
- Targeting Fibronectin to Overcome Remyelination Failure in Multiple Sclerosis: The Need for Brain- and Lesion-Targeted Drug Delivery.International journal of molecular sciences · 2022Review
- Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in the hippocampus of lithium-pilocarpine-induced acute epileptic rats.Molecular biology reports · 2022Article
- Regulatory Cells in Multiple Sclerosis: From Blood to Brain.Biomedicines · 2022Review
- Dynamics of Microglia Activation in the Ischemic Brain: Implications for Myelin Repair and Functional Recovery.Frontiers in cellular neuroscience · 2022Review
- The molecular regulation of oligodendrocyte development and CNS myelination by ECM proteins.Frontiers in cell and developmental biology · 2022Review
- Macroglial diversity: white and grey areas and relevance to remyelination.Cellular and molecular life sciences : CMLS · 2021Review
- Increased matrix metalloproteinases in cerebrospinal fluids of patients with major depressive disorder and schizophrenia.The international journal of neuropsychopharmacology · 2020Article
- Review
- Oncostatin M-induced astrocytic tissue inhibitor of metalloproteinases-1 drives remyelination.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Regulation of Oligodendrocyte Functions: Targeting Lipid Metabolism and Extracellular Matrix for Myelin Repair.Journal of clinical medicine · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Upon demyelination, transient expression of fibronectin precedes successful remyelination. However, in chronic demyelination observed in multiple sclerosis (MS), aggregates of fibronectin persist and contribute to remyelination failure. Accordingly, removing fibronectin (aggregates) would constitute an effective strategy for promoting remyelination. Matrix metalloproteinases (MMPs) are enzymes known to remodel extracellular matrix components, including fibronectin. Here, we examined the ability of MMPs to degrade fibronectin aggregates. Our findings reveal that MMP7 cleaved fibronectin aggregates resulting into a prominent 13 kDa EIIIA (16 kDa EDA)-containing fragment. MMP7 was upregulated during lysolecithin-induced demyelination, indicating its potential for endogenous fibronectin clearance. In contrast, the expression of proMMP7 was substantially decreased in chronic active and inactive MS lesions compared with control white matter and remyelinated MS lesions. Microglia and macrophages were major cellular sources of proMMP7 and IL-4-activated, but not IFNγ+LPS-activated, microglia and macrophages secreted significant levels of proMMP7. Also, conditioned medium of IL-4-activated macrophages most efficiently cleaved fibronectin aggregates upon MMP-activating conditions. Yet, coatings of MMP7-cleaved fibronectin aggregate fragments inhibited oligodendrocyte maturation, indicating that further degradation and/or clearance by phagocytosis is essential. These findings suggest that MMP7 cleaves fibronectin aggregates, while reduced (pro)MMP7 levels in MS lesions contribute to their persistent presence. Therefore, upregulating MMP7 levels may be key to remove remyelination-impairing fibronectin aggregates in MS lesions.
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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.