Matrix metalloproteinase (MMP) system in brain: identification and characterization of brain‐specific MMP highly expressed in cerebellum

Abstract

The matrix metalloproteinase (MMP) family, comprising more than 20 isoforms, modulates the extracellular milieu by degrading extracellular matrix (ECM) proteins. Because MMP is one of the few groups of proteinases capable of hydrolysing insoluble fibrillar proteins, they are likely to play crucial roles in regulating both normal and pathophysiological processes in the brain. However, little is yet known about their possible neuronal functions due presumably to their unusual redundancy and to the absence of a complete catalogue of isoforms. As an initial step in understanding the MMP system in the brain, we analysed an expression spectrum of MMP in rat brain using RT-PCR and discovered a novel brain-specific MMP, MT5-MMP. MT5-MMP was the predominant species among the nongelatinase-type isoforms in brain. MT5-MMP, present in all brain tissues examined, was most strongly expressed in cerebellum and was localized in the membranous structures of expressing neurons, as assessed biochemically and immunohistochemically. In cerebellum, its expression was regulated developmentally and was closely associated with dendritic tree formation of Purkinje cells, suggesting that MT5-MMP may contribute to neuronal development. Furthermore, its stable postdevelopmental expression and colocalization with senile plaques in Alzheimer brain indicates possible roles in neuronal remodeling naturally occurring in adulthood and in regulating pathophysiological processes associated with advanced age.

Tissue mRNA expression in rat of newly described matrix metalloproteinases

“…After cDNA normalization other tissues showed comparable MMP-24 mRNA expression levels, such as in bone and kidney. Our observations in the CNS are in line with previous reports of high MMP-24 expression in the rodent brain (Jaworski, 2000;Sekine-Aizawa et al, 2001;Nuttall et al, 2004). There are, however, some discrepancies with previous observations in rat since no remarkable mRNA expression of MMP-24 has been detected in lung or kidney before (Jaworski, 2000;SekineAizawa et al, 2001).…”

Inhibition of Angiogenic Properties of Brain Endothelial Cells by Platelet-Derived Sphingosine-1-Phosphate

“…Other MT-MMPs have been shown to be expressed in a tissuedependent manner. For instance, MT5-MMP have been described as being mainly expressed in brain (Hayashita-Kinoh et al, 2001;Sekine-Aizawa et al, 2001). Thus, assessing the roles of other MT-MMPs, and more particularly MT5-MMP, in cerebral EC should certainly provide new insights in our understanding of the major role that these proteins play in brain angiogenesis.…”

The Expression of Matrix Metalloproteinase-12 by Oligodendrocytes Regulates Their Maturation and Morphological Differentiation

“…MMP activity is required for neurite extension (Zuo et al, 1998;Webber et al, 2002) in which the mechanism may similarly involve the MMP-mediated degradation of inhibitory proteoglycans (Zuo et al, 1998). Further supporting the concept of beneficial properties of MMPs is the knowledge that many MMP members are elevated during CNS development (Canete Soler et al, 1995a,b;Vaillant et al, 1999;Sekine-Aizawa et al, 2001). Understanding the role of these proteases during development may shed light on the beneficial components of MMPs required to achieve recovery from pathological conditions.…”