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微小 RNA-145 的过表达通过靶向脑缺血性脑卒中的水通道蛋白 4 减轻星形胶质细胞损伤。

Overexpression of MicroRNA-145 Ameliorates Astrocyte Injury by Targeting Aquaporin 4 in Cerebral Ischemic Stroke.

机构信息

Department of Neurology, The Puren Hospital, Wuhan University of Science and Technology, Wuhan 430081, China.

出版信息

Biomed Res Int. 2017;2017:9530951. doi: 10.1155/2017/9530951. Epub 2017 Sep 13.

Abstract

Cerebral ischemic stroke, which affects the global population, is a major disease with high incidence, mortality, and disability. Accumulating evidence has indicated that abnormal microRNA (miRNA) expression plays essential roles in the pathologies of ischemic stroke. Yet, the underlying regulatory mechanism of miRNAs in cerebral ischemic stroke remains unclear. We investigated the role of miR-145 in cerebral ischemic stroke and its potential mechanism in a model using primary cultured astrocytes. We detected the expression levels of miR-145 and its target gene and assessed the role of miR-145 in cell death and apoptosis caused by oxygen-glucose deprivation (OGD). Bioinformatics analysis was used to explore the targets of miR-145. miR-145 expression levels were significantly decreased in primary astrocytes subjected to OGD. miR-145 overexpression promoted astrocyte health and inhibited OGD-induced apoptosis. was a direct target of miR-145, and miR-145 suppressed expression. Moreover, AQP4 enhanced astrocyte injury in ischemic stroke, and AQP4 knockdown diminished the miR-145-mediated protective effect on ischemic injury. Taken together, our results show that miR-145 plays an important role in protecting astrocytes from ischemic injury by downregulating expression. These findings may highlight a novel therapeutic target in cerebral ischemic stroke.

摘要

脑缺血性脑卒中影响全球人群,是一种具有高发病率、死亡率和致残率的主要疾病。越来越多的证据表明,异常的 microRNA(miRNA)表达在缺血性脑卒中的病理中起着重要作用。然而,miRNA 在脑缺血性脑卒中的潜在调节机制仍不清楚。我们在原代培养的星形胶质细胞模型中研究了 miR-145 在脑缺血性脑卒中的作用及其潜在机制。我们检测了 miR-145 及其靶基因的表达水平,并评估了 miR-145 在氧葡萄糖剥夺(OGD)引起的细胞死亡和凋亡中的作用。生物信息学分析用于探索 miR-145 的靶基因。在 OGD 处理的原代星形胶质细胞中,miR-145 的表达水平显著降低。miR-145 过表达促进了星形胶质细胞的健康,并抑制了 OGD 诱导的凋亡。AQP4 是 miR-145 的直接靶基因,miR-145 抑制了 AQP4 的表达。此外,AQP4 增强了缺血性脑卒中期间的星形胶质细胞损伤,而 AQP4 的敲低减少了 miR-145 对缺血性损伤的保护作用。总之,我们的研究结果表明,miR-145 通过下调 AQP4 的表达在保护星形胶质细胞免受缺血性损伤方面发挥着重要作用。这些发现可能突出了脑缺血性脑卒中的一个新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2f8/5615955/5bb4ea8e166c/BMRI2017-9530951.001.jpg

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