miR-141-3p protects against blood-brain barrier disruption and brain injury after intracerebral hemorrhage by targeting ZEB2.

MicroRNAs (miRNAs) participate in the diagnosis and treatment of intracerebral hemorrhage (ICH). miR-141-3p has been widely reported to regulate neurological disorders and cerebropathy. However, the specific role of miR-141-3p in ICH has not yet been revealed. The aim of this study was exploration of the biological functions and mechanism of miR-141-3p in ICH by establishing a collagenase-induced ICH mouse model. After ICH induction, miR-141-3p mimics or miR-NC were administered into the right striatum of the model mice followed by the performance of neurological tests. After euthanasia of the mice, the injury volume, brain water content, and injury to the blood-brain barrier (BBB) were evaluated. Evans blue (EB) was used to stain the brain slices, and EB extravasation was detected to evaluate the injury to BBB. miR-141-3p expression in perihematomal edema and hematoma areas after ICH was assessed by RT-qPCR. The levels of tight junction proteins in brain tissues and human brain microvascular endothelial cells (BMECs) were evaluated by western blotting. The FITC-dextran 20 method was used to assess BMEC permeability. The binding between miR-141-3p and zinc finger E-box-binding homeobox 2 (ZEB2) was verified with a luciferase reporter assay. In this study, miR-141-3p overexpression alleviated ICH-induced brain injury and protected BBB integrity in vivo. ZEB2 was a target gene of miR-141-3p. ZEB2 overexpression promoted BBB disruption, and miR-141-3p overexpression attenuated the promoting effect exerted by ZEB2. Overall, miR-141-3p protects against BBB disruption and attenuates brain injuries induced by ICH by targeting ZEB2. Copyright © 2022 Elsevier Ltd. All rights reserved.

Citation

Miao Yu, Tian Tian, Jiwei Zhang, Tiemin Hu. miR-141-3p protects against blood-brain barrier disruption and brain injury after intracerebral hemorrhage by targeting ZEB2. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2022 May;99:253-260

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PMID: 35306455

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