Laboratory of Hygienic Sciences, Kobe Pharmaceutical University, Kobe, Japan.
Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo, Japan.
Neurosci Lett. 2020 Nov 20;739:135406. doi: 10.1016/j.neulet.2020.135406. Epub 2020 Sep 25.
A strong therapeutic target of ischemic stroke is controlling brain inflammation. Recent studies have implicated the critical role of C-C chemokine receptor 5 (CCR5) in neuroinflammation during ischemic stroke. It has been reported that the expression of the matrix metalloproteinases, MMP-3, MMP-12, and MMP-13, is controlled by CCR5; however, their expressional regulation in the infarct brain has not been clearly understood. This study investigated the mRNA expression of Mmp-3, -12, and -13 in the ischemic cerebral cortex of photothrombosis mouse model. The three Mmps were highly upregulated in the early stages of ischemic stroke and were expressed in different types of cells. Mmp-3 and Mmp-13 were expressed in blood vessel endothelial cells after ischemia-induction, whereas Mmp-12 was expressed in activated microglia. The expression of Mmp-13 in resting microglia and in neurons of uninjured cerebral cortex was lost in the infarct region. Therefore, the MMPs responding to CCR5 are differentially regulated during ischemic stroke.
脑缺血后控制脑内炎症是一个强有力的治疗靶点。最近的研究表明，趋化因子 C-C 受体 5（CCR5）在脑缺血后的神经炎症中起关键作用。有报道称，基质金属蛋白酶 MMP-3、MMP-12 和 MMP-13 的表达受 CCR5 调控，但它们在梗死脑组织中的表达调控尚不清楚。本研究通过光血栓形成小鼠模型，研究了 MMP-3、-12 和 -13 在缺血性大脑皮质中的 mRNA 表达。这三种 MMP 在缺血性卒中的早期阶段高度上调，并在不同类型的细胞中表达。MMP-3 和 MMP-13 在缺血诱导后血管内皮细胞中表达，而 MMP-12 在激活的小胶质细胞中表达。在梗死区域，静息小胶质细胞和未受损大脑皮层神经元中的 MMP-13 表达缺失。因此，在缺血性卒中期间，对 CCR5 有反应的 MMP 受到不同的调控。
