Department of Neurology, Puai Hospital of Tongji Medical College, Huazhong University of Science and Technology Wuhan 430033, PR China.
Brain Res Bull. 2013 May;94:56-62. doi: 10.1016/j.brainresbull.2013.02.007. Epub 2013 Mar 7.
Matrix metallinoprotease-9 (MMP9) plays a key role in the pathogenesis of post-ischemic blood brain barrier (BBB) disruption and the formation of lesions after cerebral ischemia. In this study we investigate the effect of brain-specific miRNAs on MMP-9 protein level in the rat hippocampus following cerebral ischemia and its underlying mechanism. Cerebral ischemia significantly upregulated miR-21 and -224 in the hippocampus; however, expression of miR-122 and -338-3p was not significantly affected by ischemia. Silencing of miR-21, but not -224, reduced MMP9 protein level after cerebral ischemia. Downregulation of extracellular signal-regulated kinase (ERK) signaling using the ERK inhibitor U0126 and the calcium-channel blocker ketamine inhibited the upregulation of miR-21 expression and MMP9 protein level after cerebral ischemia. The study suggests that cerebral ischemia up-regulates expression level of miR-21, which is involved in ERK-stimulated upregulation of MMP9 following cerebral ischemia via a calcium-dependent mechanism.
基质金属蛋白酶-9（MMP9）在缺血后血脑屏障（BBB）破坏和脑缺血后病变的形成中起关键作用。在这项研究中，我们研究了脑特异性 miRNA 对脑缺血后大鼠海马 MMP-9 蛋白水平的影响及其潜在机制。脑缺血显著上调了海马中的 miR-21 和 -224；然而，miR-122 和 -338-3p 的表达不受缺血的显著影响。沉默 miR-21 而不是 -224 可降低脑缺血后的 MMP9 蛋白水平。使用 ERK 抑制剂 U0126 和钙通道阻滞剂氯胺酮下调细胞外信号调节激酶（ERK）信号可抑制脑缺血后 miR-21 表达和 MMP9 蛋白水平的上调。该研究表明，脑缺血上调了 miR-21 的表达水平，通过钙依赖机制，miR-21 参与了 ERK 刺激的脑缺血后 MMP9 的上调。
