Hongsheng Ding1, Shan Gao2, Lei Wang3, Yan Wei3, Meiyun Zhang3. 1. Department of Neurology, Tianjin Union Medical Center, Tianjin, China. Electronic address: huansong789@163.com. 2. Department of Neurology, ShangHai Jiaotong University affiliated the Sixth People Hospital, Shanghai, China. 3. Department of Neurology, Tianjin Union Medical Center, Tianjin, China.
Abstract
OBJECTIVE: The purpose of this study was to explore the role of miR-582-5p/proteinase-activated receptors type I (PAR-1)/Rho/Rho in neuronal cell apoptosis after cerebral ischemic stroke (CIS). METHODS: In vivo mouse model of CIS induced by middle cerebral artery occlusion and in vitro model induced by oxygen-glucose deprivation/reoxygenation (OGD/R) in N2A cells was established. The expressions of miR-582-5p, PAR-1, RhoA, and ROCKII in brain tissues and N2A cells were detected. Neuronal cell apoptosis was detected by flow cytometry. RESULTS: We found that miR-582-5p expression was decreased and the expressions of PAR-1, RhoA, and ROCKII were increased in CIS mice and OGD/R model. Moreover, miR-582-5p negatively regulated PAR-1, and overexpression of miR-582-5p inhibited the activation of Rho/Rho pathway by downregulating PAR-1, thus reducing OGD/R-induced neuronal cell apoptosis. CONCLUSIONS: Our results suggested that miR-582-5p overexpression could regulate Rho/Rho-kinase signaling pathway via targeting PAR-1, thereby governing the apoptosis of neuronal cells after CIS.
OBJECTIVE: The purpose of this study was to explore the role of miR-582-5p/proteinase-activated receptors type I (PAR-1)/Rho/Rho in neuronal cell apoptosis after cerebral ischemic stroke (CIS). METHODS: In vivo mouse model of CIS induced by middle cerebral artery occlusion and in vitro model induced by oxygen-glucose deprivation/reoxygenation (OGD/R) in N2A cells was established. The expressions of miR-582-5p, PAR-1, RhoA, and ROCKII in brain tissues and N2A cells were detected. Neuronal cell apoptosis was detected by flow cytometry. RESULTS: We found that miR-582-5p expression was decreased and the expressions of PAR-1, RhoA, and ROCKII were increased in CIS mice and OGD/R model. Moreover, miR-582-5p negatively regulated PAR-1, and overexpression of miR-582-5p inhibited the activation of Rho/Rho pathway by downregulating PAR-1, thus reducing OGD/R-induced neuronal cell apoptosis. CONCLUSIONS: Our results suggested that miR-582-5p overexpression could regulate Rho/Rho-kinase signaling pathway via targeting PAR-1, thereby governing the apoptosis of neuronal cells after CIS.