MiR-182 Inhibition Protects Against Experimental Stroke in vivo and Mitigates Astrocyte Injury and Inflammation in vitro via Modulation of Cortactin Activity.
MiR-182 Inhibition Protects Against Experimental Stroke in vivo and Mitigates Astrocyte Injury and Inflammation in vitro via Modulation of Cortactin Activity.
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DOI：
10.1007/s11064-022-03718-6
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发表时间：
2022-12
影响因子：
4.4
通讯作者：
Stary, Creed M.
中科院分区：
文献类型：
--
作者：
Alhadidi, Qasim M.;Xu, Lijun;Sun, Xiaoyun;Althobaiti, Yusuf S.;Almalki, Atiah;Alsaab, Hashem O.;Stary, Creed M.
缺血性中风仍然是一种毁灭性的脑血管疾病，在全世界造成的死亡和残疾中所占比例很高。MicroRNAs （miRNAs）是一类负责调控转录后基因表达的小非编码rna，越来越多的证据支持miRNAs在卒中损伤和恢复中的作用。目前的研究通过体外和体内缺血性损伤模型研究了miR-182在实验性卒中中的作用。在小鼠的短暂性大脑中动脉闭塞（MCAO）和受氧-葡萄糖剥夺/再灌注（OGD/R）联合损伤的原代星形胶质细胞培养物中，miR-182的脑水平显著升高。在体内，miR-182安塔戈米尔预处理显著改善了脑卒中容量和神经学评分。在OGD/R胁迫下培养的星形胶质细胞导致线粒体断裂和皮质蛋白（一种肌动蛋白结合蛋白）的下调。抑制miR-182可显著保护皮质蛋白的表达，减少线粒体断裂，提高OGD/R后星形胶质细胞的存活率。与此同时，抑制miR-182显著减少了脂多糖（LPS）诱导的星形胶质细胞中一氧化氮的释放，从而减少了LPS处理的星形胶质细胞在条件培养基中培养的原代神经元的损伤。这些发现确定了miR-182和/或皮质蛋白是保留线粒体结构和减轻缺血性卒中后神经炎症和细胞死亡的潜在临床靶点。
Ischemic stroke remains a devastating cerebrovascular disease that accounts for a high proportion of mortality and disability worldwide. MicroRNAs (miRNAs) are a class of small non-coding RNAs that are responsible for regulation of post-transcriptional gene expression, and growing evidence supports a role for miRNAs in stroke injury and recovery. The current study examined the role of miR-182 in experimental stroke using both in vitro and in vivo models of ischemic injury. Brain levels of miR-182 significantly increased after transient middle cerebral artery occlusion (MCAO) in mice and in primary astrocyte cultures subjected to combined oxygen–glucose deprivation/reperfusion (OGD/R) injury. In vivo, stroke volume and neurological score were significantly improved by pre-treatment with miR-182 antagomir. Astrocyte cultures stressed with OGD/R resulted in mitochondrial fragmentation and downregulation of cortactin, an actin-binding protein. Inhibition of miR-182 significantly preserved cortactin expression, reduced mitochondrial fragmentation and improved astrocyte survival after OGD/R. In parallel, lipopolysaccharide (LPS)-induced nitric-oxide release in astrocyte cultures was significantly reduced by miR-182 inhibition, translating to reduced injury in primary neuronal cultures subjected to conditioned medium from LPS-treated astrocytes. These findings identify miR-182 and/or cortactin as potential clinical targets to preserve mitochondrial structure and mitigate neuroinflammation and cell death after ischemic stroke.
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DOI：
10.1186/s13046-018-0824-1
发表时间：
2018-07-09
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Li Y;Zhang H;Gong H;Yuan Y;Li Y;Wang C;Li W;Zhang Z;Liu M;Liu H;Chen J
通讯作者：
Chen J
影响因子：
38.1
作者：
Bhalala, Oneil G.;Srikanth, Maya;Kessler, John A.
通讯作者：
Kessler, John A.
影响因子：
24.5
作者：
Blaya, Delia;Coll, Mar;Sancho-Bru, Pau
通讯作者：
Sancho-Bru, Pau
影响因子：
2.9
作者：
Hyun, Hye-Won;Min, Su-Ji;Kim, Ji-Eun
通讯作者：
Kim, Ji-Eun
影响因子：
9.3
作者：
Ibanez, Francesc;Montesinos, Jorge;Pascual, Maria
通讯作者：
Pascual, Maria