The MMP-1/PAR-1 Axis Enhances Proliferation and Neuronal Differentiation of Adult Hippocampal Neural Progenitor Cells

Neural Plasticity
Maria Maddalena ValenteMariagrazia Grilli

Abstract

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 ef...Continue Reading

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Citations

Dec 22, 2017·International Journal of Molecular Sciences·Santina ChiechioMariagrazia Grilli
Jun 7, 2019·Cellular and Molecular Life Sciences : CMLS·Anna BerounLeszek Kaczmarek
Nov 21, 2019·Cells·Lauren Eric Swenarchuk
May 5, 2017·Neural Regeneration Research·Valeria Bortolotto, Mariagrazia Grilli
Oct 2, 2019·Frontiers in Pharmacology·Valeria BortolottoMariagrazia Grilli
Dec 12, 2019·Frontiers in Pharmacology·Simona Federica SpampinatoMariagrazia Grilli
Mar 2, 2021·Neural Regeneration Research·Valeria BortolottoMariagrazia Grilli
Nov 18, 2020·Brain Research Bulletin·Mingyue WangDongdong Qin

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Methods Mentioned

BETA
Assay
protein assay
dissection
FCS
Nuclear Translocation
flow cytometry

Software Mentioned

FCS express

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