Cellular Neurosciences, Max Delbrück Centre for Molecular Medicine, Berlin, Germany; Department of Neurology, Charité, Universitätsmedizin Berlin, Charité Campus Virchow, Berlin, Germany.
J Neurosci Res. 2014 Mar;92(3):275-86. doi: 10.1002/jnr.23288. Epub 2013 Dec 9.
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.
我们之前曾报道过，神经胶质瘤细胞可诱导肿瘤相关的小胶质细胞/巨噬细胞中膜型 1 基质金属蛋白酶（MT1-MMP 或 MMP-14）的表达，并促进肿瘤生长，而生理条件下小胶质细胞中 MMP-14 的表达水平非常低。在这里，我们发现 MMP-14 的表达增加也存在于与神经退行性和神经炎症性疾病相关的小胶质细胞/巨噬细胞中，无论是在小鼠模型中，还是在人类活检或尸检组织中。我们发现，阿尔茨海默病组织、多发性硬化症的活动病变以及 II 期中风组织以及相应的人类疾病的小鼠模型中，小胶质细胞/巨噬细胞 MMP-14 的表达上调。相比之下，我们在中风的早期阶段或相应的小鼠模型中、在人类肌萎缩侧索硬化症（ALS）组织或 ALS 的小鼠模型中以及在人类急性脑外伤病例中均未观察到小胶质细胞/巨噬细胞中 MMP-14 的上调。这些数据表明，MMP-14 的表达不是激活的小胶质细胞/巨噬细胞的一般标志物，而是在神经炎症和神经退行性疾病的特定阶段上调，并且在小鼠模型和人类脑病理之间通常存在很好的匹配。
