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

Djoere Gaublomme, Tom Buyens, Lies De Groef, Michelle Stakenborg, Els Janssens, Signe Ingvarsen, Astrid Porse, Niels Behrendt, Lieve Moons

    26 Citationer (Scopus)

    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.

    OriginalsprogEngelsk
    TidsskriftJournal of Neurochemistry
    Vol/bind129
    Udgave nummer6
    Sider (fra-til)966-79
    ISSN0022-3042
    DOI
    StatusUdgivet - 27 mar. 2014

    Fingeraftryk

    Dyk ned i forskningsemnerne om 'Matrix metalloproteinase 2 and membrane-type 1 matrix metalloproteinase co-regulate axonal outgrowth of mouse retinal ganglion cells'. Sammen danner de et unikt fingeraftryk.

    Citationsformater