ZEB2, interacting with MDM2, contributes to the dysfuntion of brain microvascular endothelial cells and brain injury after intracerebral hemorrhage

Guo, Qingbao; Xie, Manli; Guo, Miao; Yan, Feiping; Li, Lihong; Li, Rui

doi:10.1080/15384101.2021.1959702

Cited by 5 publications

(2 citation statements)

References 34 publications

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“…Afterwards, 4 μL of LV-shLCN2 lentivirus or LV-NC lentivirus was injected into the right lateral cerebral cortex motor area of the ICH rats by using a 5-µL Hamilton syringe at a rate of 1 µL/min. 27 Neurobehavioral deficits were examined at 72 h after injection. Subsequently, blood samples were obtained from rats.…”

Section: Methodsmentioning

confidence: 99%

Knockdown of LCN2 Attenuates Brain Injury After Intracerebral Hemorrhage via Suppressing Pyroptosis

Zhao,

Xiao,

Sun

et al. 2024

NDT

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Objective The aims of this study are to screen novel differentially expressed genes (DEGs) for intracerebral hemorrhage (ICH) and reveal the role of Lipocalin-2 (LCN2) in ICH. Methods We constructed the ICH model by injection of autologous whole blood into the right basal ganglia in rats. RNA-sequencing and bioinformatics analyses were performed to identify the DEGs between ICH and sham rats, and some important ones were confirmed using quantitative real-time PCR (qRT-PCR). LCN shRNA was used to knockdown of LCN2 in ICH rats. Pathological examination was carried out using 2,3,5-triphenyltetrazolium chloride (TTC) staining and Hematoxylin-eosin (HE) staining. Immunohistochemistry detected Caspase-3, and co-staining of Terminal dUTP nick end labeling (TUNEL) and NEUN staining were performed for neuron apoptosis assessment. Western blot analysis was performed to quantify pyroptosis-related proteins. Enzyme-linked immunosorbent assay (ELISA) was used to measure inflammatory cytokine levels. Results ICH rats exhibited significant hematomas, higher brain water content, obvious interstitial edema, and inflammatory infiltration, as well as more apoptotic cells in brain tissues. RNA-seq analysis identified 103 upregulated and 81 downregulated DEGs. The expression of LCN2, HSPB1, CXCL10, and MEF2B were upregulated in ICH rats. ICH triggered the release of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and IL-18, and promoted the expression of pyroptosis-related proteins Caspase-1, GSDMD, NLRP3, and ASC. LCN2 knockdown attenuated the pathological characteristics of ICH, and also reduced pyroptosis in brain tissues. Conclusion Inhibition of LCN2 attenuates brain injury after ICH via suppressing pyroptosis, which provide guidance for ICH management.

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Section: Methodsmentioning

confidence: 99%

Knockdown of LCN2 Attenuates Brain Injury After Intracerebral Hemorrhage via Suppressing Pyroptosis

Zhao,

Xiao,

Sun

et al. 2024

NDT

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“…For in vitro ICH model construction, BMECs were treated with iron hemoglobin at a concentration of 10 μ M [ 14 ] (ICH group) and blank control (blank). Then, the ICH cells were transfected with negative control (ICH+NC), silencing RNA BCL-3 (ICH+siRNA BCL-3), vector (ICH+vector), BCL-3 overexpression plasmid (ICH+BCL-3), and an agonist 2-C1HA (ICH+siRNA BCL-3+2-C1HA) by using Lipofectamine ® 2000 (Invitrogen; Thermo Fisher Scientific, Inc.) at 37°C for 2 days.…”

Section: Methodsmentioning

confidence: 99%

BCL-3 Promotes Intracerebral Hemorrhage Progression by Increasing Blood–Brain Barrier Permeability, Inflammation, and Cell Apoptosis via Endoplasmic Reticulum Stress

Yin,

Ran,

Luo

et al. 2023

Mediators of Inflammation

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Background. Intracerebral hemorrhage (ICH) is among the common types of stroke with high mortality and morbidity. Molecular biomarker selection is crucial for ICH diagnosis and treatment. However, the identification of ICH-related biomarkers remains inadequate. Materials and Methods. In vivo and in vitro ICH models were generated and transfected with silenced B-cell lymphoma-3 (BCL-3 and siRNA BCL-3), overexpressed BCL-3, and endoplasmic reticulum stress (ERS) agonist (2-CLHA). Hematoxylin–eosin staining and transmission electron microscopy were used to observe the transfected cells. RNA sequencing was performed in vivo on the sham and ICH groups. The blood–brain barrier (BBB) permeability was evaluated by determining Evans blue dye extravasation, transendothelial electrical resistance, and paracellular permeability. Moreover, tight junction-, cell apoptosis-, and endoplasmic reticulum stress- (ERS-) related proteins were evaluated through real-time quantitative PCR, western blotting, immunohistochemistry, and TUNEL staining. The levels of inflammatory cytokines were measured through the enzyme-linked immunosorbent assay. Results. RNA-seq revealed that BCL-3 acts as a key player. BCL-3 promotes ICH progression by increasing BBB permeability, ERS, inflammation, and cell apoptosis. Silencing of BCL-3 slows ICH progression by reducing BBB permeability and inflammation and terminating cell apoptosis and ERS in vitro and in vivo. Conclusion. Our study identified ICH biomarkers and elucidated the role of BCL-3 in ICH for the first time.

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

Tian

Zhang

et al. 2022

Journal of Clinical Neuroscience

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ZEB2, interacting with MDM2, contributes to the dysfuntion of brain microvascular endothelial cells and brain injury after intracerebral hemorrhage

Cited by 5 publications

References 34 publications

Knockdown of LCN2 Attenuates Brain Injury After Intracerebral Hemorrhage via Suppressing Pyroptosis

Knockdown of LCN2 Attenuates Brain Injury After Intracerebral Hemorrhage via Suppressing Pyroptosis

BCL-3 Promotes Intracerebral Hemorrhage Progression by Increasing Blood–Brain Barrier Permeability, Inflammation, and Cell Apoptosis via Endoplasmic Reticulum Stress

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

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