A New Role for TIMP-1 in Modulating Neurite Outgrowth and Morphology of Cortical Neurons
| Autor: | Ould-Yahoui, A, Tremblay, E, Sbai, O, Ferhat, L, Bernard, A, Charrat, E, Gueye, Y, Lim, NH, Brew, K, Risso, J-J, Dive, V, Khrestchatisky, M, Rivera, S, Chédotal, A |
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| Přispěvatelé: | Chédotal, A |
| Rok vydání: | 2016 |
| Předmět: |
Neurite
Cell Survival Recombinant Fusion Proteins Central nervous system Green Fluorescent Proteins Growth Cones lcsh:Medicine Biology Matrix Metalloproteinase Inhibitors Inhibitory postsynaptic potential Gene Expression Regulation Enzymologic Paracrine signalling Mice medicine Extracellular Neurites Animals Humans Enzyme Inhibitors lcsh:Science Growth cone Cytoskeleton Cell Shape Cells Cultured Cerebral Cortex Multidisciplinary Tissue Inhibitor of Metalloproteinase-1 Neuroscience/Neuronal and Glial Cell Biology lcsh:R Neuroscience/Neurodevelopment Actins Cell biology Cytoskeletal Proteins medicine.anatomical_structure Matrix Metalloproteinase 9 Cerebral cortex lcsh:Q Mutant Proteins Neuroscience/Neurobiology of Disease and Regeneration Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 4, Iss 12, p e8289 (2009) |
| Popis: | Background Tissue inhibitor of metalloproteinases-1 (TIMP-1) displays pleiotropic activities, both dependent and independent of its inhibitory activity on matrix metalloproteinases (MMPs). In the central nervous system (CNS), TIMP-1 is strongly upregulated in reactive astrocytes and cortical neurons following excitotoxic/inflammatory stimuli, but no information exists on its effects on growth and morphology of cortical neurons. Principal Findings We found that 24 h incubation with recombinant TIMP-1 induced a 35% reduction in neurite length and significantly increased growth cones size and the number of F-actin rich microprocesses. TIMP-1 mediated reduction in neurite length affected both dendrites and axons after 48 h treatment. The effects on neurite length and morphology were not elicited by a mutated form of TIMP-1 inactive against MMP-1, -2 and -3, and still inhibitory for MMP-9, but were mimicked by a broad spectrum MMP inhibitor. MMP-9 was poorly expressed in developing cortical neurons, unlike MMP-2 which was present in growth cones and whose selective inhibition caused neurite length reductions similar to those induced by TIMP-1. Moreover, TIMP-1 mediated changes in cytoskeleton reorganisation were not accompanied by modifications in the expression levels of actin, βIII-tubulin, or microtubule assembly regulatory protein MAP2c. Transfection-mediated overexpression of TIMP-1 dramatically reduced neuritic arbour extension in the absence of detectable levels of released extracellular TIMP-1. Conclusions Altogether, TIMP-1 emerges as a modulator of neuronal outgrowth and morphology in a paracrine and autrocrine manner through the inhibition, at least in part, of MMP-2 and not MMP-9. These findings may help us understand the role of the MMP/TIMP system in post-lesion pre-scarring conditions. |
| Databáze: | OpenAIRE |
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