| Matrix metalloproteases and their inhibitors are produced by overlapping populations of activated astrocytes. | |
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MedLine Citation:
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PMID: 12008026 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Matrix metalloproteases (MMPs) and tissue inhibitors of metalloproteases (TIMPs) are involved in many cell migration phenomena and produced by many cell types, including neurons and glia. To assess their possible roles in brain injury and regeneration, we investigate their production by glial cells, after brain injury and in tissue culture, and we investigate whether they are capable of digesting known axon-inhibitory proteoglycans. To determine the action of MMPs, we incubated astrocyte conditioned medium with activated MMPs, then did western blots for several chondroitin sulphate proteoglycans. MMP-3 digested all five proteoglycans tested, whereas MMP-2 digested only two and MMP-9 none. To determine whether MMPs or TIMPs are produced by astrocytes in vitro, we tested both primary cultures and astrocyte cell lines by western blotting, and compared them with Schwann cells. All cultures produced at least some MMPs and TIMPs, with no obvious correlation with the ability of axons to grow on those cells. Both MMP-9 and TIMP-3 were regulated by various cytokines. To determine which cells produce MMPs and TIMPs after brain injury, we made lesions of adult rat cortex, and did immunohistochemistry. MMP-2 was seen to be induced in activated astrocytes through the whole thickness of the cortex but not deeper, but MMP-3 was not seen in the injured brain. TIMP-2 and TIMP-3 immunoreactivities were induced in activated astrocytes in deep cortex and the underlying white matter. In situ hybridisation confirmed induction of TIMP-2 in glia as well as neurons, but showed no expression of TIMP-4. These results show that both MMPs and TIMPs are produced by some astrocytes, but TIMP production is particularly strong, especially in deep cortex and white matter which is more inhibitory for axon regeneration. Conversely the MMPs produced may not be adequate to promote migration of cells and axons within the glial scar. |
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Authors:
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E M Muir; K H Adcock; D A Morgenstern; R Clayton; N von Stillfried; K Rhodes; C Ellis; J W Fawcett; J H Rogers |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Brain research. Molecular brain research Volume: 100 ISSN: 0169-328X ISO Abbreviation: Brain Res. Mol. Brain Res. Publication Date: 2002 Apr |
Date Detail:
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Created Date: 2002-05-14 Completed Date: 2002-08-13 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8908640 Medline TA: Brain Res Mol Brain Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 103-17 Citation Subset: IM |
Affiliation:
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Department of Physiology, University of Cambridge, Cambridge CB2 3EG, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Antibody Specificity Astrocytes / cytology, enzymology* Brain / enzymology*, pathology, physiopathology Brain Injuries / enzymology*, pathology, physiopathology Cells, Cultured Cerebral Cortex / enzymology, injuries, physiopathology Cytokines / metabolism, pharmacology Gliosis / enzymology*, pathology, physiopathology Growth Cones / enzymology In Situ Hybridization Matrix Metalloproteinase 2 / drug effects, metabolism Matrix Metalloproteinase 3 / genetics, metabolism Matrix Metalloproteinase 9 / drug effects, metabolism Matrix Metalloproteinases / genetics, metabolism* Nerve Regeneration / physiology* Proteochondroitin Sulfates / metabolism RNA, Messenger / metabolism Rats Tissue Inhibitor of Metalloproteinase-2 / genetics, metabolism Tissue Inhibitor of Metalloproteinase-3 / drug effects, metabolism Tissue Inhibitor of Metalloproteinases / genetics, metabolism* Up-Regulation / physiology |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Proteochondroitin Sulfates; 0/RNA, Messenger; 0/Tissue Inhibitor of Metalloproteinase-3; 0/Tissue Inhibitor of Metalloproteinases; 0/tissue inhibitor of metalloproteinase-4; 127497-59-0/Tissue Inhibitor of Metalloproteinase-2; EC 3.4.24.-/Matrix Metalloproteinases; EC 3.4.24.17/Matrix Metalloproteinase 3; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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