title: Membrane-type 1 metalloproteinase is upregulated in microglia/brain macrophages in neurodegenerative and neuroinflammatory diseases.
abstract: We previously reported that glioma cells induce the expression of membrane-type 1 metalloproteinase (MT1-MMP or MMP-14) in tumor-associated microglia/macrophages and promote tumor growth, whereas MMP-14 expression in microglia under physiological conditions is very low. Here, we show that the increase in MMP-14 expression is also found in microglia/macrophages associated with neurodegenerative and neuroinflammatory pathologies in mouse models as well as in human biopsies or post-mortem tissue. We found that microglial/macrophage MMP-14 expression was upregulated in Alzheimer's disease tissue, in active lesions of multiple sclerosis, and in tissue from stage II stroke as well as in the corresponding mouse models for the human diseases. In contrast, we observed no upregulation for MMP-14 in microglia/macrophages in the early phase of stroke or in the corresponding mouse model, in human amyotrophic lateral sclerosis (ALS) tissue or in a mouse model of ALS as well as in human cases of acute brain trauma. These data indicate that MMP-14 expression is not a general marker for activated microglia/macrophages but is upregulated in defined stages of neuroinflammatory and neurodegenerative diseases and that there is generally a good match between mouse models and human brain pathologies.
authors: Cellular Neurosciences, Max Delbrück Centre for Molecular Medicine, Berlin, Germany; Department of Neurology, Charité, Universitätsmedizin Berlin, Charité Campus Virchow, Berlin, Germany.
authors: Anika
authors: A
authors: Langenfurth
authors: Jan Leo
authors: JL
authors: Rinnenthal
authors: Katyayni
authors: K
authors: Vinnakota
authors: Vincent
authors: V
authors: Prinz
authors: Anne-Sophie
authors: AS
authors: Carlo
authors: Christine
authors: C
authors: Stadelmann
authors: Volker
authors: V
authors: Siffrin
authors: Susann
authors: S
authors: Peaschke
authors: Matthias
authors: M
authors: Endres
authors: Frank
authors: F
authors: Heppner
authors: Rainer
authors: R
authors: Glass
authors: Susanne A
authors: SA
authors: Wolf
authors: Helmut
authors: H
authors: Kettenmann
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004660:Encephalitis / Q000209:etiology / Q000473:pathology*; D005910:Glioma / Q000150:complications / Q000473:pathology; D006801:Humans; D008264:Macrophages / Q000201:enzymology*; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins; D017628:Microglia / Q000201:enzymology*; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000473:pathology*; D015854:Up-Regulation / Q000502:physiology*; D014951:Wounds, Stab / Q000150:complications / Q000473:pathology
chemical_list: C112986:AIF1 protein, human; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D053511:Matrix Metalloproteinase 14
keywords: Alzheimer's disease; MMP-14; MT1-MMP; amyotrophic lateral sclerosis; macrophages; metalloproteinase; microglia; multiple sclerosis; neurodegeneration; neuroinflammation; stroke; trauma