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Matrix metalloproteinase 2 and membrane-type 1 matrix metalloproteinase co-regulate axonal outgrowth of mouse retinal ganglion cells

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Gaublomme, Djoere ; Buyens, Tom ; De Groef, Lies ; Stakenborg, Michelle ; Janssens, Els ; Ingvarsen, Signe ; Porse, Astrid ; Behrendt, Niels ; Moons, Lieve. / Matrix metalloproteinase 2 and membrane-type 1 matrix metalloproteinase co-regulate axonal outgrowth of mouse retinal ganglion cells. I: Journal of Neurochemistry. 2014 ; Bind 129, Nr. 6. s. 966-79.

Bibtex

@article{d295aa0d3cc0463b891d5311024d3020,
title = "Matrix metalloproteinase 2 and membrane-type 1 matrix metalloproteinase co-regulate axonal outgrowth of mouse retinal ganglion cells",
abstract = "Restoration of correct neural activity following central nervous system (CNS) damage requires the replacement of degenerated axons with newly outgrowing, functional axons. Unfortunately, spontaneous regeneration is largely lacking in the adult mammalian CNS. In order to establish successful regenerative therapies, an improved understanding of axonal outgrowth and the various molecules influencing it, is highly needed. Matrix metalloproteinases (MMPs) constitute a family of zinc-dependent proteases that were sporadically reported to influence axon outgrowth. Using an ex vivo retinal explant model, we were able to show that broad-spectrum MMP inhibition reduces axon outgrowth of mouse retinal ganglion cells (RGCs), implicating MMPs as beneficial factors in axonal regeneration. Additional studies, using more specific MMP inhibitors and MMP-deficient mice, disclosed that both MMP-2 and MT1-MMP, but not MMP-9, are involved in this process. Furthermore, administration of a novel antibody to MT1-MMP that selectively blocks proMMP-2 activation revealed a functional co-involvement of these proteinases in determining RGC axon outgrowth. Subsequent immunostainings showed expression of both MMP-2 and MT1-MMP in RGC axons and glial cells. Finally, results from combined inhibition of MMP-2 and β1-integrin were suggestive for a functional interaction between these molecules.",
author = "Djoere Gaublomme and Tom Buyens and {De Groef}, Lies and Michelle Stakenborg and Els Janssens and Signe Ingvarsen and Astrid Porse and Niels Behrendt and Lieve Moons",
note = "This article is protected by copyright. All rights reserved.",
year = "2014",
month = "3",
day = "27",
doi = "10.1111/jnc.12703",
language = "English",
volume = "129",
pages = "966--79",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "6",

}

RIS

TY - JOUR

T1 - Matrix metalloproteinase 2 and membrane-type 1 matrix metalloproteinase co-regulate axonal outgrowth of mouse retinal ganglion cells

AU - Gaublomme, Djoere

AU - Buyens, Tom

AU - De Groef, Lies

AU - Stakenborg, Michelle

AU - Janssens, Els

AU - Ingvarsen, Signe

AU - Porse, Astrid

AU - Behrendt, Niels

AU - Moons, Lieve

N1 - This article is protected by copyright. All rights reserved.

PY - 2014/3/27

Y1 - 2014/3/27

N2 - Restoration of correct neural activity following central nervous system (CNS) damage requires the replacement of degenerated axons with newly outgrowing, functional axons. Unfortunately, spontaneous regeneration is largely lacking in the adult mammalian CNS. In order to establish successful regenerative therapies, an improved understanding of axonal outgrowth and the various molecules influencing it, is highly needed. Matrix metalloproteinases (MMPs) constitute a family of zinc-dependent proteases that were sporadically reported to influence axon outgrowth. Using an ex vivo retinal explant model, we were able to show that broad-spectrum MMP inhibition reduces axon outgrowth of mouse retinal ganglion cells (RGCs), implicating MMPs as beneficial factors in axonal regeneration. Additional studies, using more specific MMP inhibitors and MMP-deficient mice, disclosed that both MMP-2 and MT1-MMP, but not MMP-9, are involved in this process. Furthermore, administration of a novel antibody to MT1-MMP that selectively blocks proMMP-2 activation revealed a functional co-involvement of these proteinases in determining RGC axon outgrowth. Subsequent immunostainings showed expression of both MMP-2 and MT1-MMP in RGC axons and glial cells. Finally, results from combined inhibition of MMP-2 and β1-integrin were suggestive for a functional interaction between these molecules.

AB - Restoration of correct neural activity following central nervous system (CNS) damage requires the replacement of degenerated axons with newly outgrowing, functional axons. Unfortunately, spontaneous regeneration is largely lacking in the adult mammalian CNS. In order to establish successful regenerative therapies, an improved understanding of axonal outgrowth and the various molecules influencing it, is highly needed. Matrix metalloproteinases (MMPs) constitute a family of zinc-dependent proteases that were sporadically reported to influence axon outgrowth. Using an ex vivo retinal explant model, we were able to show that broad-spectrum MMP inhibition reduces axon outgrowth of mouse retinal ganglion cells (RGCs), implicating MMPs as beneficial factors in axonal regeneration. Additional studies, using more specific MMP inhibitors and MMP-deficient mice, disclosed that both MMP-2 and MT1-MMP, but not MMP-9, are involved in this process. Furthermore, administration of a novel antibody to MT1-MMP that selectively blocks proMMP-2 activation revealed a functional co-involvement of these proteinases in determining RGC axon outgrowth. Subsequent immunostainings showed expression of both MMP-2 and MT1-MMP in RGC axons and glial cells. Finally, results from combined inhibition of MMP-2 and β1-integrin were suggestive for a functional interaction between these molecules.

U2 - 10.1111/jnc.12703

DO - 10.1111/jnc.12703

M3 - Journal article

VL - 129

SP - 966

EP - 979

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 6

ER -

ID: 43824264