MicroRNA-193b-3p alleviates focal cerebral ischemia and reperfusion-induced injury in rats by inhibiting 5-lipoxygenase expression

Chen, Zhihao; Yang, Junqing; Zhong, Jian; Luo, Ying; Du, Weiming; Hu, Congli; Xia, Hui; Li, Yuke; Zhang, Jiahua; Li, Miaomiao; Yang, Yang; Huang, Haifeng; Peng, Zhe; Tan, Xiaodan; Wang, Hong

doi:10.1016/j.expneurol.2020.113223

Cited by 32 publications

(18 citation statements)

References 34 publications

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“…Oxygen-Glucose Deprivation/Reoxygenation (OGD/R) for in vitro Cerebral I/R OGD/R has been recognized as an in vitro model for simulating I/R injury (Chen et al, 2020). PC12 cells have been widely used in neurophysiological and pathological research (Koubi et al, 2005).…”

Section: Cell Culturementioning

confidence: 99%

Exosomes Secreted From Bone Marrow Mesenchymal Stem Cells Attenuate Oxygen-Glucose Deprivation/Reoxygenation-Induced Pyroptosis in PC12 Cells by Promoting AMPK-Dependent Autophagic Flux

Zeng

Zhou

Liang

et al. 2020

Front. Cell. Neurosci.

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Background : Cerebral ischemia–reperfusion (I/R) injury can lead to severe dysfunction, and its treatment is difficult. It is reported that nucleotide-binding domain and leucine-rich repeat family protein 3 (NLRP3) inflammasome-mediated cell pyroptosis is an important part of cerebral I/R injury and the activation of autophagy can inhibit pyroptosis in some tissue injury. Our previous study found that the protective effects of bone marrow mesenchymal stem cells (BMSCs) in cerebral I/R injury may be associated with the regulation of autophagy. Recent studies have demonstrated that exosomes secreted from BMSCs (BMSC-Exos) may play an essential role in the effective biological performance of BMSCs and the protective mechanism of BMSC-Exos is associated with the activation of autophagy and the remission of inflammation, but it has not been reported in studies of cerebral I/R injury. We aimed to investigate the effects of BMSC-Exos on cerebral I/R injury and determine if the mechanism is associated with the regulation of pyroptosis and autophagic flux. Method : PC12 cells were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to induce cerebral I/R in vitro and were cocultured with BMSC-Exos. Cell viability was determined with CCK-8 and lactate dehydrogenase (LDH) detection kits. Scanning electron microscopy (SEM), Hoechst 33342/propidium iodide (PI) double staining, 2′,7′-dichlorodihydrofluorescein diacetate assay, immunofluorescence, Western blot, and Enzyme-linked immunosorbent assay (ELISA) were used to detect cell pyroptosis. Furthermore, transmission electron microscopy (TEM), GFP-RFP-LC3 adenovirus transfection, and Western blot were used to detect autophagic flux and its influence on pyroptosis. Finally, coimmunoprecipitation was used to detect the binding interaction between NLRP3 and LC3. Results : BMSC-Exos increased cell viability in OGD/R. The inhibitory effect of BMSC-Exos on pyroptosis was comparable to the NLRP3 inhibitor MCC950 and was reversed by NLRP3 overexpression. Furthermore, BMSC-Exos promoted autophagic flux through the AMP-activated kinase (AMPK)/mammalian target of the rapamycin pathway, whereas chloroquine, AMPK silencing, and compound C blocked the inhibitory effect on pyroptosis. Conclusions : BMSC-Exos can protect PC12 cells against OGD/R injury via attenuation of NLRP3 inflammasome-mediated pyroptosis by promoting AMPK-dependent autophagic flux.

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Section: Cell Culturementioning

confidence: 99%

Exosomes Secreted From Bone Marrow Mesenchymal Stem Cells Attenuate Oxygen-Glucose Deprivation/Reoxygenation-Induced Pyroptosis in PC12 Cells by Promoting AMPK-Dependent Autophagic Flux

Zeng

Zhou

Liang

et al. 2020

Front. Cell. Neurosci.

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“…MiR-674-5p can attenuate concanavalin A-induced liver injury in mice by downregulating 5-LOX ( 117 ). In rats with focal cerebral ischemia and reperfusion, miRNA-193b-3p can alleviate the injury by inhibiting the expression of 5-LOX ( 118 ). In a deficient mouse model, a decrease of let-7 miRNAs led to the upregulation of 5-LOX and subsequent aberrant activation of the leukotriene biosynthesis pathway in Drosha mutants ( 119 ).…”

Section: Mirnas Regulating the Synthesis Of Leukotrienesmentioning

confidence: 99%

miRNAs and Leukotrienes in Respiratory Syncytial Virus Infection

Fan

et al. 2021

Front. Pediatr.

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MicroRNAs (miRNAs) are small, non-coding RNAs that regulate posttranscription by binding to 3′-untranslated regions of target mRNAs. Recent functional studies have elucidated mechanisms that miRNAs regulate leukotriene synthesis by perturbing arachidonic acid metabolism. Both microarrays and high-throughput sequencing revealed distinct differential expression of miRNAs in children with respiratory syncytial virus (RSV) infection compared with healthy controls. Abnormal miRNA expression may contribute to higher leukotriene levels, which is associated with airway hyperreactivity. Targeting miRNAs may benefit to restore the homeostasis of inflammatory reaction and provide new strategies to alleviate airway hyperreactivity induced by RSV. In this article, we provide an overview of the current knowledge about miRNAs modulating leukotrienes through regulation of arachidonic acid metabolism with a special focus on miRNAs aberrantly expressed in children with RSV infection.

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“…3 However, restoration of blood flow unavoidably generates pathological damage in the ischemic brain tissue, ultimately leads to the cerebral ischemia/reperfusion (I/R) injury. 4 Since numerous mechanisms, such as cell toxicity, apoptosis, oxidative stress and inflammation are found to be involved in cerebral I/R injury, 5 the pathogenesis of stroke is extremely complex. 6 Therefore, the development of new drugs may be beneficial for the treatment of IS.…”

Section: Introductionmentioning

confidence: 99%

Physcion Protects Rats Against Cerebral Ischemia-Reperfusion Injury via Inhibition of TLR4/NF-kB Signaling Pathway

Dong

Wang

Song

et al. 2021

DDDT

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Background Ischemic stroke (IS) is characterized by the rapid loss of brain function due to ischemia. Physcion has been found to have a neuroprotective effect against cerebral ischemia-reperfusion (I/R) injury. However, the mechanism by which physcion regulates cerebral I/R injury remains largely unknown. Methods An oxygen-glucose deprivation/reperfusion (OGD/R) model in SH-SY5Y cells and a rat cerebral ischemia-reperfusion (I/R) model were established, respectively. CCK-8 and flow cytometry assays were used to detect the viability and apoptosis of SH-SY5Y cells. Moreover, enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of SOD, MDA, GSH-Px, TNF-α, IL-1β, IL-6 and IL-10 in the supernatant of SH-SY5Y cells. Meanwhile, Western blot assay was used to detect the expressions of TLR4, p-p65 and p-IκB in SH-SY5Y cells and I/R rats. Results In this study, physcion treatment significantly rescued OGD/R-induced neuronal injury. In addition, physcion decreased inflammatory response in SH-SY5Y cells after OGD/R insult, as shown by the decreased levels of the pro-inflammatory factors TNF-α, IL-1β, IL-6 and IL-10. Moreover, physcion attenuated the oxidative stress in OGD/R-treated SY-SY5Y cells, as evidenced by the increased SOD and GSH levels and the decreased ROS and MDA levels. Meanwhile, physcion significantly reduced cerebral infarction, attenuated neuronal injury and apoptosis in I/R rats. Furthermore, physcion markedly decreased the expressions of TLR4, p-NF-κB p65 and p-IκB in the brain tissues of rats subjected to I/R and in SH-SY5Y cells exposed to OGD/R. Conclusion In conclusion, our study indicated that physcion protected neuron cells against I/R injury in vitro and in vivo by inhibition of the TLR4/NF-kB pathway; thus, physcion might serve as a promising therapeutic candidate for IS.

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MicroRNA-193b-3p alleviates focal cerebral ischemia and reperfusion-induced injury in rats by inhibiting 5-lipoxygenase expression

Cited by 32 publications

References 34 publications

Exosomes Secreted From Bone Marrow Mesenchymal Stem Cells Attenuate Oxygen-Glucose Deprivation/Reoxygenation-Induced Pyroptosis in PC12 Cells by Promoting AMPK-Dependent Autophagic Flux

Exosomes Secreted From Bone Marrow Mesenchymal Stem Cells Attenuate Oxygen-Glucose Deprivation/Reoxygenation-Induced Pyroptosis in PC12 Cells by Promoting AMPK-Dependent Autophagic Flux

miRNAs and Leukotrienes in Respiratory Syncytial Virus Infection

Physcion Protects Rats Against Cerebral Ischemia-Reperfusion Injury via Inhibition of TLR4/NF-kB Signaling Pathway

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