Elevated expression of membrane type I metalloproteinase (MT1-MMP) in reactive astrocytes following neurodegeneration in mouse central nervous system

Reactive astrocytes occurring in response to neurodegeneration are thought to play an important role in neuronal regeneration by upregulating the expr ession of extracellular matrix (ECM) components as well as the ECM degradin g metalloproteinases (MMPs). We examined the mRNA levels and cellular distr ibution of membrane type matrix metalloproteinase 1 (MT1-MMP) and tissue in hibitors 1-4 of MMPs (TIMPs) in brain stem and spinal cord of wobbler (WR) mutant mice affected by progressive neurodegeneration and astrogliosis. MT1 -MMP, TIMP-1 and TIMP-3 mRNA levels were elevated, whereas TIMP-2 and TIMP- 4 expression was not affected. MT1-MMP was expressed in reactive astrocytes of WR. In primary astrocyte cultures, MT1-MMP mRNA was upregulated by exog eneous tumor necrosis factor alpha. Increased plasma membrane and secreted MMP activities were found in primary WR astrocytes. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All righ ts reserved.