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KMID : 1034820230190030425
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Molecular & Cellular Toxicology
2023 Volume.19 No. 3 p.425 ~ p.436
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MiR-370-3p aggravates blood?brain barrier injury and neuron apoptosis by targeting SMURF1 to activate the TLR4/MyD88/NF-κB signaling in sepsis-associated encephalopathy
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Neng Wang
Dan Zhong
Jie Lin
Jennifer Jooha Lee
Yu Chen
Lili Wang
Mei Chen
Cong Luo
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Abstract
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Background : Sepsis-associated encephalopathy (SAE) is characterized by blood?brain barrier (BBB) disruption, neuron apoptosis and inflammation. Studies show that miR-370-3p can be a new diagnostic biomarker for SAE.
Objective : This study aims to investigate the role of miR-370-3p in SAE and the underlying mechanism.
Result : An in vitro model of BBB disruption was established in brain microvascular endothelial cells (BMECs) with lipopolysaccharide (LPS). The expression level of RNAs was tested via RT-qPCR. Protein levels were detected by western blotting. Annexin V/PI double staining and CCK-8 assays were conducted to assess the apoptosis and viability of brain microvascular endothelial cells (BMECs). The migration of BMECs was detected by Transwell assay. BBB permeability analysis was performed to assess the relative permeability coefficient of BMECs. The in vitro barrier integrity was detected by trans-epithelial/endothelial electrical resistance (TEER). The binding between miR-370-3p and SMAD specific E3 ubiquitin protein ligase 1 (SMURF1) was identified by luciferase reporter assay. In this study, miR-370-3p was upregulated in LPS-treated BMECs. MiR-370-3p knockdown alleviated LPS-induced BBB disruption and apoptosis of BMECs, as well as recovered cell viability and migration. SMURF1 was directly targeted by miR-370-3p. SMURF1 silencing reversed the effects of miR-370-3p deficiency in LPS-stimulated BMECs. Moreover, miR-370-3p activated the TLR4/MyD88/NF-κB signaling via regulating SMURF1 in LPS-stimulated BMECs.
Conclusion : MiR-370-3p aggravates BBB disruption and neuron apoptosis by targeting SMURF1 to activate the TLR4/MyD88/NF-κB signaling in SAE.
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KEYWORD
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SAE, miR-370-3p, SMURF1, BBB, BMECs
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