LncRNA H19 promotes inflammatory response induced by cerebral ischemia–reperfusion injury through regulating the miR-138-5p–p65 axis

2020 ◽  
Vol 98 (4) ◽  
pp. 525-536
Author(s):  
Hui Li ◽  
Chenglu Tang ◽  
Dan Wang
Keyword(s):  
Cerebral Ischemia ◽  
Inflammatory Response ◽  
Rat Model ◽  
In Vitro Model ◽  
Ischemia Reperfusion ◽  
Neurological Function ◽  
Cerebral Ischemia Reperfusion ◽  
Vitro Model

Recent studies have shown that long non-coding RNA(LncRNA) H19 is up-regulated in the brain of rats suffering from cerebral ischemia–reperfusion (I/R) injury, inducing severe disability and mortality. Little was known about the molecular mechanisms underlying the involvement of H19 in cerebral I/R injury. In this study, a rat model of I/R was induced by transient middle cerebral artery occlusion (tMCAO). PC-12 cells exposed to oxygen and glucose deprivation/reoxygenation (OGD/R) were used as an in vitro model. Our results show that H19 is up-regulated in both in vivo and in our in vitro model. Further study indicated that knockdown of H19 promotes cell proliferation, decreases the rate of cell apoptosis, and ameliorates inflammation after OGD/R simulation. Our in vivo study shows that H19 knockdown ameliorates inflammation and improves neurological function in our rat model of tMCAO. Remarkably, the results from our luciferase reporter assays suggest that H19 negatively regulates the expression of miR-138-5p, and p65 was identified as a target of miR-138-5p. To sum up, this study demonstrated that H19 promotes an inflammatory response and improves neurological function in a rat model of tMCAO by regulating the expression of miR-138-5p and p65. This study reveals the important role and underlying mechanism of H19 in the progress of cerebral I/R injury, which could serve as a potential target for further treatment.

scholarly journals Adrenomedullin expression in a rat model of acute lung injury induced by hypoxia and LPS

2005 ◽  
Vol 288 (3) ◽  
pp. L536-L545 ◽  
Author(s):  
Jackeline Agorreta ◽  
Javier J. Zulueta ◽  
Luis M. Montuenga ◽  
Mercedes Garayoa
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Cell Lines ◽  
Rat Model ◽  
In Vitro Model ◽  
Rat Lung ◽  
Vitro Model

Adrenomedullin (ADM) is upregulated independently by hypoxia and LPS, two key factors in the pathogenesis of acute lung injury (ALI). This study evaluates the expression of ADM in ALI using experimental models combining both stimuli: an in vivo model of rats treated with LPS and acute normobaric hypoxia (9% O2) and an in vitro model of rat lung cell lines cultured with LPS and exposed to hypoxia (1% O2). ADM expression was analyzed by in situ hybridization, Northern blot, Western blot, and RIA analyses. In the rat lung, combination of hypoxia and LPS treatments overcomes ADM induction occurring after each treatment alone. With in situ techniques, the synergistic effect of both stimuli mainly correlates with ADM expression in inflammatory cells within blood vessels and, to a lesser extent, to cells in the lung parenchyma and bronchiolar epithelial cells. In the in vitro model, hypoxia and hypoxia + LPS treatments caused a similar strong induction of ADM expression and secretion in epithelial and endothelial cell lines. In alveolar macrophages, however, LPS-induced ADM expression and secretion were further increased by the concomitant exposure to hypoxia, thus paralleling the in vivo response. In conclusion, ADM expression is highly induced in a variety of key lung cell types in this rat model of ALI by combination of hypoxia and LPS, suggesting an essential role for this mediator in this syndrome.

scholarly journals OM-MSCs Alleviate the Golgi Apparatus Stress Response following Cerebral Ischemia/Reperfusion Injury via the PEDF-PI3K/Akt/mTOR Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Jialin He ◽  
Jianyang Liu ◽  
Yan Huang ◽  
Xiangqi Tang ◽  
Han Xiao ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Stress Response ◽  
Cerebral Ischemia ◽  
Stress Responses ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

The mechanism of Golgi apparatus (GA) stress responses mediated by GOLPH3 has been widely studied in ischemic stroke, and the neuroprotection effect of olfactory mucosa mesenchymal stem cells (OM-MSCs) against cerebral ischemia/reperfusion injury (IRI) has been preliminarily presented. However, the exact role of OM-MSCs in the GA stress response following cerebral IRI remains to be elucidated. In the present study, we used an oxygen-glucose deprivation/reoxygenation (OGD/R) model and reversible middle cerebral artery occlusion (MCAO) model to simulate cerebral IRI in vitro and in vivo. Our results showed that the level of GOLPH3 protein, reactive oxygen species (ROS), and Ca2+ was upregulated, SPCA1 level was downregulated, and GA fragmentation was increased in ischemic stroke models, and OM-MSC treatment clearly ameliorated these GA stress responses in vitro and in vivo. Subsequently, the knockdown of PEDF in OM-MSCs using PEDF-specific siRNA further demonstrated that secretion of PEDF in OM-MSCs protected OGD/R-treated N2a cells and MCAO rats from GA stress response. Additionally, rescue experiment using specific pathway inhibitors suggested that OM-MSCs could promote the phosphorylation of the PI3K/Akt/mTOR pathway, thereby mitigating OGD/R-induced GA stress response and excessive autophagy. In conclusion, OM-MSCs minimized the GA stress response following cerebral IRI, at least partially, through the PEDF-PI3K/Akt/mTOR pathway.

scholarly journals Neuroprotective effect of Indobufen against pyroptosis following cerebral ischemia-reperfusion injury both in vivo and in vitro

2020 ◽  
Author(s):  
Tian Zhang ◽  
Dan Xu ◽  
Fengyang Li ◽  
Rui Liu ◽  
Kai Hou ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Umbilical Vein ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Therapeutic Effects ◽  
Caspase 1 ◽  
Cerebral Ischemia Reperfusion

Abstract Background: Indobufen is a new generation of antiplatelet agents and has been shown to have antithrombotic effects in animal models. However, the efficacy of Indobufen on cerebral ischemia/reperfusion (I/R) injury and its mechanisms remain to be investigated. Methods: In this study, the efficacy of Indobufen with both pre- (5days) and post- (15days) treatment on rats suffering middle cerebral artery occlusion/reperfusion (MCAO/R, 2h of ischemia and 24h/15days of reperfusion) was investigated. Furthermore, human umbilical vein endothelial cells (HUVECs) were cultured and underwent oxygen glucose deprivation/reoxygenation (OGD/R) injury for in vitro studies. Relationship between Indobufen and pyroptosis associated NF-κB/Caspase-1/GSDMD pathway was preliminarily discussed. Results: The pharmacodynamic tests revealed that Indobufen ameliorated I/R injury by decreasing the platelet aggregation, infarct size, brain edema and neurologic impairment in rats and rescuing cell apoptosis/pyroptosis in HUVECs. The underlying mechanisms were probably related to pyroptosis suppression by platelet inhibition induced regulation of the NF-κB/Caspase-1/GSDMD pathway.Conclusion: Overall, these studies indicates that Indobufen exerts protective and therapeutic effects against I/R injury by pyroptosis suppression via downregulating NF-κB/Caspase-1/GSDMD pathway.

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