MiR-195-5p Ameliorates Cerebral Ischemia-Reperfusion Injury by Regulating the PTEN-AKT Signaling Pathway

Abstract

Background 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.

Neuroprotective Effect of Daidzein Extracted From Pueraria lobate Radix in a Stroke Model Via the Akt/mTOR/BDNF Channel

“…Moreover, p-CREB is involved in neuronal apoptosis processes, which is mediated partially by BDNF. p-CREB overexpression inhibited neuronal apoptosis, whereas the inhibition of CREB activity accelerated neuronal apoptosis (Ren et al, 2021).…”

“…According to another study, mTOR signal pathway achieved a vital function for protection against ischemic stroke (Li et al, 2021b). Moreover, Ren et al, confirmed that PI3K/Akt/mTOR signaling pathway could protect nerve energy cells by participating in oxidative stress and negatively regulating apoptosis (Ren et al, 2021). Consistent results were achieved here, which demonstrated that daidzein significantly up-regulated the expression levels of p-PI3K, p-Akt and p-mTOR, while LY294002, a specific inhibitor of PI3K, noticeably reversed the aforementioned effects of daidzein.…”

The mechanism of sevoflurane post-treatment alleviating hypoxic-ischemic encephalopathy by affecting histone methyltransferase G9a in rats

“…HIE can lead to neurodevelopmental and cognitive impairment in survivors, with or without motor impairment [ 5 ] and is considered to be the main cause of neonatal death [ 24 , 25 ]. SF pre-treatment and post-treatment can protect the brain [ 9 ], but the neuroprotective effect of SF pretreatment on HIE is limited [ 26 ].…”

“…Then, the sections were dehydrated with ethanol gradient, cleared with xylene, and sealed with sealing resin (YT2494, YITA Biotechnology Co., Ltd, Beijing, China). Morphological image analysis system JD801 (JD801, Jeda Technology Co. Ltd., Nanjing, China) was used to observe the morphological changes of neurons after HE staining in cerebral cortex of different groups of rats, and the images were randomly collected [ 24 , 25 ].…”

miR‑363‑3p attenuates the oxygen‑glucose deprivation/reoxygenation‑induced neuronal injury in vitro by targeting PDCD6IP

“…For instance, Wang et al ( 12 ) elucidated that miR-186-5p was upregulated and induced apoptosis in an oxygen and glucose deprivation/reperfusion (OGD/R) model by targeting insulin-like growth factor (IGF)-1. Conversely, Ren et al ( 13 ) reported that overexpression of miR-195-5p efficiently enhanced cell viability, while it reduced lactate dehydrogenase (LDH) release and the apoptotic rate in OGD-treated endothelial cells by targeting PTEN. In addition, miR-124-5p could reduce ROS production and improve the inflammatory microenvironment to attenuate cerebral I/R injury by targeting NOX2 ( 14 ).…”