Abstract
BackgroundInflammation and apoptosis are considered to be two main factors affecting ischemic brain injury and the subsequent reperfusion damage. MiR-19a-3p has been reported to be a possible novel biomarker in ischemic stroke. However, the function and molecular mechanisms of miR-19a-3p remain unclear in cerebral ischemia/reperfusion (I/R) injury.MethodsThe I/R injury model was established in vivo by middle cerebral artery occlusion/reperfusion (MCAO/R) in rats and in vitro by oxygen–glucose deprivation and reperfusion (OGD/R) induced SH-SY5Y cells. The expression of miR-19a-3p was determined by reverse transcription quantitative PCR. The infarction volumes, Neurological deficit scores, apoptosis, cell viability, pro-inflammatory cytokines and apoptosis were evaluated using Longa score, Bederson score, TTC, TUNEL staining, CCK-8, ELISA, flow cytometry assays. Luciferase reporter assay was utilized to validate the target gene of miR-19a-3p.ResultsWe first found miR-19a-3p was significantly up-regulated in rat I/R brain tissues and OGD/R induced SH-SY5Y cells. Using the in vivo and in vitro I/R injury model, we further demonstrated that miR-19a-3p inhibitor exerted protective role against injury to cerebral I/R, which was reflected by reduced infarct volume, improved neurological outcomes, increased cell viability, inhibited inflammation and apoptosis. Mechanistically, miR-19a-3p binds to 3′UTR region of IGFBP3 mRNA. Inhibition of miR-19a-3p caused the increased expression of IGFBP3 in OGD/R induced SH-SY5Y cells. Furthermore, we showed that IGFBP3 overexpression imitated, while knockdown reversed the protective effects of miR-19a-3p inhibitor against OGD/R-induced injury.ConclusionsIn summary, our findings showed miR-19a-3p regulated I/R-induced inflammation and apoptosis through targeting IGFBP3, which might provide a potential therapeutic target for cerebral I/R injury.
Highlights
Inflammation and apoptosis are considered to be two main factors affecting ischemic brain injury and the subsequent reperfusion damage
We investigated the role of miR-19a-3p in inflammation and apoptosis in middle cerebral artery occlusion (MCAO) rat model and in vitro oxygen and glucose deprivation/reoxygenation (OGD/R) induced SH-SY5Y cell model
Down‐regulation of miR‐19a‐3p protected rat brain against cerebral I/R injury To investigate the potential role of miR-19a-3p in brain I/R injury, the rats randomly received an intracerebroventricular injection of miR-19a-3p inhibitor prior to MCAO treatment, with Sham as control
Summary
Inflammation and apoptosis are considered to be two main factors affecting ischemic brain injury and the subsequent reperfusion damage. MiR-19a-3p has been reported to be a possible novel biomarker in ischemic stroke. Chai et al Biol Res (2020) 53:17 the inflammation and apoptosis are considered to be main factors inducing nerve cell injury after I/R [3,4,5,6]. With the development of ischemic stroke studies, investigation of the role of miRs in cerebral I/R injury has been increased. MiR-132 has been reported to attenuate cerebral injury by protecting blood–brain barrier disruption in ischemia stroke [10]. MiR-224-3p may protect N2a cells from cerebral I/R injury by targeting FAK familyinteracting protein (FIP200) [11]. The possible mechanisms of miR19a-3p against inflammation and apoptosis in cerebral I/R injury are still understudied
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
