Neuropsychiatric Disease and Treatment (Apr 2021)
MiR-195-5p Ameliorates Cerebral Ischemia-Reperfusion Injury by Regulating the PTEN-AKT Signaling Pathway
Abstract
Xiaoli Ren,1 Zhiyun Wang,1 Congfang Guo2 1Department of Neurology, Tianjin First Central Hospital, Tianjin, 300192, People’s Republic of China; 2Department of Emergency, Tianjin First Central Hospital, Tianjin, 300192, People’s Republic of ChinaCorrespondence: Zhiyun WangDepartment of Neurology, Tianjin First Central Hospital, No. 24 Fukang Road, Nankai District, Tianjin, 300192, People’s Republic of ChinaEmail [email protected]: MiR-195-5p has been shown to play crucial roles in tumor inhibition, but its biological functions in cerebral ischemia-reperfusion (I/R) injury are unclear.Methods: To mimic cerebral I/R injury, mice were induced by transient middle cerebral artery occlusion (MCAO). Human brain microvascular endothelial cells (HBMVECs) were treated with oxygen-glucose deprivation (OGD) to mimic I/R injury in vitro. The expression of miR-195-5p and PTEN was detected by qRT-PCR or Western blot. Cell viability was evaluated by CCK-8 assay. Cell apoptosis was detected by flow cytometer. Cell death was detected using specific lactate dehydrogenase (LDH) cytotoxicity kit. Infarct volume in mice brains was evaluated by TTC staining. Histopathological analysis was performed by HE staining and TUNEL staining. The interaction between miR-195-5p and PTEN was determined by TargetScan and luciferase reporter assay.Results: MiR-195-5p was significantly downregulated and PTEN was upregulated during cerebral I/R injury both in vitro and in vivo. Overexpression of miR-195-5p efficiently enhanced cell viability, while reduced LDH release and apoptotic rate of OGD-treated HBMVECs in vitro. MiR-195-5p could negatively regulate the expression of PTEN by directly binding to its 3′-UTR. Overexpression of PTEN obviously attenuated the protective effect of miR-195-5p mimics on cell viability, LDH release and apoptosis in OGD-treated HBMVECs. Meanwhile, overexpression of miR-195-5p increased the expression levels of p-AKT in OGD-treated HBMVECs, while this effect was reversed by overexpression of PTEN. Moreover, overexpression of miR-195-5p efficiently ameliorated brain injury of mice after MCAO treatment in vivo.Conclusion: Overexpression of miR-195-5p ameliorated cerebral I/R injury by regulating the PTEN-AKT signaling pathway, providing a potential therapeutic target for cerebral I/R injury.Keywords: cerebral I/R injury, miR-195-5p, PTEN, AKT signaling pathway
