ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Astrocytic tissue inhibitor of metalloproteinase-1 (TIMP-1) promotes oligodendrocyte differentiation and enhances CNS myelination.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 120 citations in OpenAlex.
- Article
- Astrocytic abnormalities in brain-specificChannels (Austin, Tex.) · 2025Article
- Focused ultrasound-induced blood-brain barrier opening promotes glioprotective phenotypes in ACSA-II+ murine astrocytes.iScience · 2025Article
- Clemastine Induces Oligodendrocyte Progenitor Pool Exhaustion and Senescence in the Context of Chronic Demyelination in a Rabbit Model.Annals of neurology · 2024Article
- The Effect of Tissue Inhibitor of Metalloproteinases on Scar Formation after Spinal Cord Injury.Cells · 2024Review
- Timp1 Deletion Induces Anxiety-like Behavior in Mice.Neuroscience bulletin · 2024Article
- The TIMP protein family: diverse roles in pathophysiology.American journal of physiology. Cell physiology · 2024Review
- Star power: harnessing the reactive astrocyte response to promote remyelination in multiple sclerosis.Neural regeneration research · 2024Review
- 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 Ties That Bind: Glial Transplantation in White Matter Ischemia and Vascular Dementia.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- Article
- Tackling the glial scar in spinal cord regeneration: new discoveries and future directions.Frontiers in cellular neuroscience · 2023Review
- Palmitoylethanolamide and White Matter Lesions: Evidence for Therapeutic Implications.Biomolecules · 2022Review
- Review
- Can the administration of platelet lysates to the brain help treat neurological disorders?Cellular and molecular life sciences : CMLS · 2022Review
- The Cellular Senescence Factor Extracellular HMGB1 Directly Inhibits Oligodendrocyte Progenitor Cell Differentiation and Impairs CNS Remyelination.Frontiers in cellular neuroscience · 2022Article
- Neuroinflammatory astrocyte subtypes in the mouse brain.Nature neuroscience · 2021Article
- Transcriptional heterogeneity between primary adult grey and white matter astrocytes underlie differences in modulation of in vitro myelination.Journal of neuroinflammation · 2020Article
- Secretome Analysis of Mesenchymal Stem Cell Factors Fostering Oligodendroglial Differentiation of Neural Stem Cells In Vivo.International journal of molecular sciences · 2020Article
- 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
6 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Tissue inhibitor of metalloproteinase-1 (TIMP-1) is an extracellular protein and endogenous regulator of matrix metalloproteinases (MMPs) secreted by astrocytes in response to CNS myelin injury. We have previously reported that adult TIMP-1 knock-out (KO) mice exhibit poor myelin repair following demyelinating injury. This observation led us to hypothesize a role for TIMP-1 in oligodendrogenesis and CNS myelination. Herein, we demonstrate that compact myelin formation is significantly delayed in TIMP-1 KO mice, a situation that coincided with dramatically reduced numbers of white matter astrocytes in the developing CNS. Analysis of differentiation in CNS progenitor cells (neurosphere) cultures from TIMP-1 KO mice revealed a specific deficit of NG2(+) oligodendrocyte progenitor cells. Application of recombinant murine TIMP-1 (rmTIMP-1) to TIMP-1 KO neurosphere cultures evoked a dose-dependent increase in NG2(+) cell numbers, while treatment with GM6001, a potent broad-spectrum MMP inhibitor did not. Similarly, administration of rmTIMP-1 to A2B5(+) immunopanned oligodendrocyte progenitors significantly increased the number of differentiated O1(+) oligodendrocytes, while antisera to TIMP-1 reduced oligodendrocyte numbers. We also determined that A2B5(+) oligodendrocyte progenitors grown in conditioned media derived from TIMP-1 KO primary glial cultures resulted in reduced differentiation of mature O1(+) oligodendrocytes. Finally, we report that addition of rmTIMP-1 to primary glial cultures resulted in a dose-dependent proliferative response of astrocytes. Together, these findings describe a previously uncharacterized role for TIMP-1 in the regulation of oligodendrocytes and astrocytes during development and provide a novel function for TIMP-1 on myelination in the developing CNS.
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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.