MiRNA-190 exerts neuroprotective effects against ischemic stroke through Rho/Rho-kinase pathway
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NEUROSCIENCE
MiRNA-190 exerts neuroprotective effects against ischemic stroke through Rho/Rho-kinase pathway Chuan Jiang 1 & Ning Dong 2 & Jianli Feng 1 & Maolin Hao 1
# Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Ischemic stroke is an urgent public health concern and one of the major causes of deaths and disabilities over the world. MicroRNA (miRNA) has become a key mediator of cerebral ischemia-reperfusion (I/R) injuries. However, whether miR-190 is involved in cerebral I/R-induced neuronal damage remains unknown. This study was to investigate the role of miR-190 in the brain I/R injury. We divided the rats into sham, I/R, control, and miR-190-mim (miR-190 mimics) groups. Quantitative real-time polymerase chain reaction (qRT-PCR), Nissl staining, flow cytometry, and western blot were conducted to examine the expression of miR-190 and cell apoptosis in different groups. The results showed that the expression of miR-190 was greatly decreased in rats suffering with I/R. Overexpression of miR-190 significantly reduced the increased neurological scores, brain water contents, infarct volumes, and neuronal apoptosis in rats suffering with I/R. In addition, we found that the expression of RhoA and Rho kinase was greatly elevated in rats suffering with I/R. Bioinformatics analysis indicated that Rho was a target of miR190. Moreover, overexpression of miR-190 significantly downregulated the increased mRNA and protein expression of Rho/Rho kinase and cell apoptosis, while inhibition of miR-190 further upregulated the increased mRNA and protein expression of Rho/ Rho kinase and cell apoptosis in rats suffering with I/R. Furthermore, knockdown of Rho significantly downregulated the increased mRNA and protein expression of Rho/Rho kinase and cell apoptosis, while these effects were inhibited by miR-190 inhibitors in rats suffering with I/R. These results indicate that miR-190 confers protection against brain I/R damage by modulating Rho/Rho-kinase signaling. Keywords Cerebral ischemic stroke . miRNA-190 . Rho/Rho kinase . Apoptosis
Introduction Ischemic stroke is an urgent public health concern and one of the major causes of deaths and disabilities over the world [12, 22]. An abnormal promotion in cell apoptosis may lead to neuronal death after acute ischemic brain injuries, but its underlying mechanism is not fully understood [6, 33]. The diagnosis of stroke depends on clinical manifestations and is * Jianli Feng [email protected] 1
Department of Neurology, Shandong Provincial Western Hospital, Shandong Provincial ENT Hospital, No.4 Duanxing West Road, Huanyin District, Jinan City 250022, Shandong Province, People’s Republic of China
2
Department of Neurology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan City 250001, Shandong Province, People’s Republic of China
confirmed by CT or magnetic resonance examination [3, 11]. The symptoms of early ischemic stroke are mild and difficult to distinguish from other neurological and nonneurological disorders, wh
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