A new role for TIMP-1 in modulating neurite outgrowth and morphology of cortical neurons.
<h4>Background</h4>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...
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Public Library of Science (PLoS)
2009-12-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0008289&type=printable |
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| author | Adlane Ould-yahoui Evelyne Tremblay Oualid Sbai Lotfi Ferhat Anne Bernard Eliane Charrat Yatma Gueye Ngee Han Lim Keith Brew Jean-Jacques Risso Vincent Dive Michel Khrestchatisky Santiago Rivera |
| author_facet | Adlane Ould-yahoui Evelyne Tremblay Oualid Sbai Lotfi Ferhat Anne Bernard Eliane Charrat Yatma Gueye Ngee Han Lim Keith Brew Jean-Jacques Risso Vincent Dive Michel Khrestchatisky Santiago Rivera |
| author_sort | Adlane Ould-yahoui |
| collection | DOAJ |
| description | <h4>Background</h4>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.<h4>Principal findings</h4>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, betaIII-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.<h4>Conclusions</h4>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. |
| format | Article |
| id | doaj-art-3a38dae2ac834489bdc38a9a2f86c9f3 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2009-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-3a38dae2ac834489bdc38a9a2f86c9f32025-08-20T02:01:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-12-01412e828910.1371/journal.pone.0008289A new role for TIMP-1 in modulating neurite outgrowth and morphology of cortical neurons.Adlane Ould-yahouiEvelyne TremblayOualid SbaiLotfi FerhatAnne BernardEliane CharratYatma GueyeNgee Han LimKeith BrewJean-Jacques RissoVincent DiveMichel KhrestchatiskySantiago Rivera<h4>Background</h4>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.<h4>Principal findings</h4>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, betaIII-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.<h4>Conclusions</h4>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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0008289&type=printable |
| spellingShingle | Adlane Ould-yahoui Evelyne Tremblay Oualid Sbai Lotfi Ferhat Anne Bernard Eliane Charrat Yatma Gueye Ngee Han Lim Keith Brew Jean-Jacques Risso Vincent Dive Michel Khrestchatisky Santiago Rivera A new role for TIMP-1 in modulating neurite outgrowth and morphology of cortical neurons. PLoS ONE |
| title | A new role for TIMP-1 in modulating neurite outgrowth and morphology of cortical neurons. |
| title_full | A new role for TIMP-1 in modulating neurite outgrowth and morphology of cortical neurons. |
| title_fullStr | A new role for TIMP-1 in modulating neurite outgrowth and morphology of cortical neurons. |
| title_full_unstemmed | A new role for TIMP-1 in modulating neurite outgrowth and morphology of cortical neurons. |
| title_short | A new role for TIMP-1 in modulating neurite outgrowth and morphology of cortical neurons. |
| title_sort | new role for timp 1 in modulating neurite outgrowth and morphology of cortical neurons |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0008289&type=printable |
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