Induced mRNA expression of matrix metalloproteinases Mmp-3, Mmp-12, and Mmp-13 in the infarct cerebral cortex of photothrombosis model mice

Induced mRNA expression of matrix metalloproteinases Mmp-3, Mmp-12, and Mmp-13 in the infarct cerebral cortex of photothrombosis model mice
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DOI:
10.1016/j.neulet.2020.135406
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发表时间:
2020-11-20
影响因子:
2.5
通讯作者:
Hasegawa, Hiroshi
Hasegawa, Hiroshi
中科院分区:
医学4区
文献类型:
--
作者:
Hohjoh, Hirofumi;Horikawa, Io;Hasegawa, Hiroshi

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缺血性中风的一个强有力的治疗目标是控制脑部炎症。最近的研究表明,C-C趋化因子受体5(CCR5)在缺血性卒中的神经炎症中起着关键作用。已有研究表明,基质金属蛋白酶-3、12、13的表达受CCR5调控,但其在脑梗塞中的表达调控尚不清楚。本研究观察了光镜下血栓形成模型小鼠缺血大脑皮层中基质金属蛋白酶-3、-12和-13mRNA的表达。这三种MMPs在缺血性卒中早期高度上调,并在不同类型的细胞中表达。MMP3和MMP13在缺血后的血管内皮细胞中表达,而MMP12在激活的小胶质细胞中表达。梗死区静息小胶质细胞和未损伤大脑皮层神经元中的基质金属蛋白酶-13表达缺失。因此,在缺血性卒中中,对CCR5有反应的MMPs受到不同的调节。
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 ischemiainduction, 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.