The MMP-1/PAR-1 Axis Enhances Proliferation and Neuronal Differentiation of Adult Hippocampal Neural Progenitor Cells
Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that play a role in varied forms of developmental and postnatal neuroplasticity. MMP substrates include protease-activated receptor-1 (PAR-1), a G-protein coupled receptor expressed in hippocampus. We examined proliferation and diffe...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2015/646595 |
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| author | Maria Maddalena Valente Megan Allen Valeria Bortolotto Seung T. Lim Katherine Conant Mariagrazia Grilli |
| author_facet | Maria Maddalena Valente Megan Allen Valeria Bortolotto Seung T. Lim Katherine Conant Mariagrazia Grilli |
| author_sort | Maria Maddalena Valente |
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| description | Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that play a role in varied forms of developmental and postnatal neuroplasticity. MMP substrates include protease-activated receptor-1 (PAR-1), a G-protein coupled receptor expressed in hippocampus. We examined proliferation and differentiation of adult neural progenitor cells (aNPCs) from hippocampi of mice that overexpress the potent PAR-1 agonist MMP-1. We found that, as compared to aNPCs from littermate controls, MMP-1 tg aNPCs display enhanced proliferation. Under differentiating conditions, these cells give rise to a higher percentage of MAP-2+ neurons and a reduced number of oligodendrocyte precursors, and no change in the number of astrocytes. The fact that these results are MMP and PAR-1 dependent is supported by studies with distinct antagonists. Moreover, JSH-23, an inhibitor of NF-κB p65 nuclear translocation, counteracted both the proliferation and differentiation changes seen in MMP-1 tg-derived NPCs. In complementary studies, we found that the percentage of Sox2+ undifferentiated progenitor cells is increased in hippocampi of MMP-1 tg animals, compared to wt mice. Together, these results add to a growing body of data suggesting that MMPs are effectors of hippocampal neuroplasticity in the adult CNS and that the MMP-1/PAR-1 axis may play a role in neurogenesis following physiological and/or pathological stimuli. |
| format | Article |
| id | doaj-art-bd08d2f57bad4d9e8dfe7bd8cf518e27 |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-bd08d2f57bad4d9e8dfe7bd8cf518e272025-02-03T01:22:34ZengWileyNeural Plasticity2090-59041687-54432015-01-01201510.1155/2015/646595646595The MMP-1/PAR-1 Axis Enhances Proliferation and Neuronal Differentiation of Adult Hippocampal Neural Progenitor CellsMaria Maddalena Valente0Megan Allen1Valeria Bortolotto2Seung T. Lim3Katherine Conant4Mariagrazia Grilli5Laboratory of Neuroplasticity, Department of Pharmaceutical Sciences, University of Piemonte Orientale “Amedeo Avogadro”, 28100 Novara, ItalyDepartment of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USALaboratory of Neuroplasticity, Department of Pharmaceutical Sciences, University of Piemonte Orientale “Amedeo Avogadro”, 28100 Novara, ItalyDepartment of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USADepartment of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USALaboratory of Neuroplasticity, Department of Pharmaceutical Sciences, University of Piemonte Orientale “Amedeo Avogadro”, 28100 Novara, ItalyMatrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that play a role in varied forms of developmental and postnatal neuroplasticity. MMP substrates include protease-activated receptor-1 (PAR-1), a G-protein coupled receptor expressed in hippocampus. We examined proliferation and differentiation of adult neural progenitor cells (aNPCs) from hippocampi of mice that overexpress the potent PAR-1 agonist MMP-1. We found that, as compared to aNPCs from littermate controls, MMP-1 tg aNPCs display enhanced proliferation. Under differentiating conditions, these cells give rise to a higher percentage of MAP-2+ neurons and a reduced number of oligodendrocyte precursors, and no change in the number of astrocytes. The fact that these results are MMP and PAR-1 dependent is supported by studies with distinct antagonists. Moreover, JSH-23, an inhibitor of NF-κB p65 nuclear translocation, counteracted both the proliferation and differentiation changes seen in MMP-1 tg-derived NPCs. In complementary studies, we found that the percentage of Sox2+ undifferentiated progenitor cells is increased in hippocampi of MMP-1 tg animals, compared to wt mice. Together, these results add to a growing body of data suggesting that MMPs are effectors of hippocampal neuroplasticity in the adult CNS and that the MMP-1/PAR-1 axis may play a role in neurogenesis following physiological and/or pathological stimuli.http://dx.doi.org/10.1155/2015/646595 |
| spellingShingle | Maria Maddalena Valente Megan Allen Valeria Bortolotto Seung T. Lim Katherine Conant Mariagrazia Grilli The MMP-1/PAR-1 Axis Enhances Proliferation and Neuronal Differentiation of Adult Hippocampal Neural Progenitor Cells Neural Plasticity |
| title | The MMP-1/PAR-1 Axis Enhances Proliferation and Neuronal Differentiation of Adult Hippocampal Neural Progenitor Cells |
| title_full | The MMP-1/PAR-1 Axis Enhances Proliferation and Neuronal Differentiation of Adult Hippocampal Neural Progenitor Cells |
| title_fullStr | The MMP-1/PAR-1 Axis Enhances Proliferation and Neuronal Differentiation of Adult Hippocampal Neural Progenitor Cells |
| title_full_unstemmed | The MMP-1/PAR-1 Axis Enhances Proliferation and Neuronal Differentiation of Adult Hippocampal Neural Progenitor Cells |
| title_short | The MMP-1/PAR-1 Axis Enhances Proliferation and Neuronal Differentiation of Adult Hippocampal Neural Progenitor Cells |
| title_sort | mmp 1 par 1 axis enhances proliferation and neuronal differentiation of adult hippocampal neural progenitor cells |
| url | http://dx.doi.org/10.1155/2015/646595 |
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