Down-Regulation of miR-181a-5p Prevents Cerebral Ischemic Injury by Upregulating En2 and Activating Wnt/β-catenin Pathway

Song, Xiaoming; Xue, Yongming; Cai, Hairui

doi:10.1016/j.jstrokecerebrovasdis.2020.105485

Cited by 12 publications

(9 citation statements)

References 32 publications

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“…Moreover, other micro-RNAs, such as miR-193, miR-126, secreted by VAT adipose tissue promote CCL2 secretion by body adipocytes, a chemokine that facilitates monocyte/macrophage infiltration in adipose tissue, cells that in turn release pro-inflammatory cytokines [270]. On the other hand, a reduction of miR-181a-5p release is associated with atherosclerotic plaque formation [314] and downregulation of miR-181a-5p also prevents cerebral ischemic injury [315] and alleviates oxidative stress and inflammation in coronary microembolization-induced myocardial damage [316]. In this context, it is also known that microRNA-23a-3p attenuates oxidative stress injury in a mouse model of focal cerebral ischemia-reperfusion [317] and microRNA-199a-3p protect cardiomyocytes from simulated ischemia-reperfusion injury [318], participating in the regulation of the NOS (NO Synthase)/NO pathway in the endothelium [319].…”

Section: Visceral Abdominal and Subcutaneous Adipose Tissuesmentioning

confidence: 99%

Physiological Changes and Pathological Pain Associated with Sedentary Lifestyle-Induced Body Systems Fat Accumulation and Their Modulation by Physical Exercise

Verdú

Homs

Boadas-Vaello

2021

IJERPH

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A sedentary lifestyle is associated with overweight/obesity, which involves excessive fat body accumulation, triggering structural and functional changes in tissues, organs, and body systems. Research shows that this fat accumulation is responsible for several comorbidities, including cardiovascular, gastrointestinal, and metabolic dysfunctions, as well as pathological pain behaviors. These health concerns are related to the crosstalk between adipose tissue and body systems, leading to pathophysiological changes to the latter. To deal with these health issues, it has been suggested that physical exercise may reverse part of these obesity-related pathologies by modulating the cross talk between the adipose tissue and body systems. In this context, this review was carried out to provide knowledge about (i) the structural and functional changes in tissues, organs, and body systems from accumulation of fat in obesity, emphasizing the crosstalk between fat and body tissues; (ii) the crosstalk between fat and body tissues triggering pain; and (iii) the effects of physical exercise on body tissues and organs in obese and non-obese subjects, and their impact on pathological pain. This information may help one to better understand this crosstalk and the factors involved, and it could be useful in designing more specific training interventions (according to the nature of the comorbidity).

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Section: Visceral Abdominal and Subcutaneous Adipose Tissuesmentioning

confidence: 99%

Physiological Changes and Pathological Pain Associated with Sedentary Lifestyle-Induced Body Systems Fat Accumulation and Their Modulation by Physical Exercise

Verdú

Homs

Boadas-Vaello

2021

IJERPH

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“…Tnf was also reported to be significantly upregulated in MCAO/R animal models and OGD/R cell models ( Li et al, 2019 ; Zhang et al, 2021a ; Zhou et al, 2021 ). Moreover, it was reported that miR-181a-5p was highly expressed in serum of ischemic stroke patients, brain tissues of MCAO/R mice, and an oxygen-glucose-deprivation/reoxygenation (OGD/R) N2a cell model ( Ouyang et al, 2012 ; Wu et al, 2017 ; Song et al, 2021 ). Studies also reported that miR-181b-5p and miR-181c-5p expression was significantly decreased in cerebral ischemia in vivo and in vitro ( Deng et al, 2016 ; Ma et al, 2016 ; Zhang et al, 2018 ; Meng et al, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies suggested that the miR-181 family participates in the regulation of a range of biological processes including cell proliferation ( Huo et al, 2016 ), apoptosis ( Zhang et al, 2018 ), autophagy ( Guo et al, 2019 ), and immune and inflammatory responses ( Hutchison et al, 2013 ; Lu et al, 2019 ). Moreover, several studies have demonstrated that the inhibition of miR-181a-5p played a neuroprotective role in cerebral ischemic injury, as evidenced by reductions in cell apoptosis, pyroptosis, and cerebral infarction area ( Moon et al, 2013 ; Stary et al, 2017 ; Yan et al, 2020 ; Song et al, 2021 ). However, the roles of miR-181b-5p and miR-181c-5p in cerebral ischemia have remained controversial.…”

Section: Discussionmentioning

confidence: 99%

Identification of programmed cell death-related gene signature and associated regulatory axis in cerebral ischemia/reperfusion injury

Shu

Wei

et al. 2022

Front. Genet.

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Background: Numerous studies have suggested that programmed cell death (PCD) pathways play vital roles in cerebral ischemia/reperfusion (I/R) injury. However, the specific mechanisms underlying cell death during cerebral I/R injury have yet to be completely clarified. There is thus a need to identify the PCD-related gene signatures and the associated regulatory axes in cerebral I/R injury, which should provide novel therapeutic targets against cerebral I/R injury.Methods: We analyzed transcriptome signatures of brain tissue samples from mice subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) and matched controls, and identified differentially expressed genes related to the three types of PCD(apoptosis, pyroptosis, and necroptosis). We next performed functional enrichment analysis and constructed PCD-related competing endogenous RNA (ceRNA) regulatory networks. We also conducted hub gene analysis to identify hub nodes and key regulatory axes.Results: Fifteen PCD-related genes were identified. Functional enrichment analysis showed that they were particularly associated with corresponding PCD-related biological processes, inflammatory response, and reactive oxygen species metabolic processes. The apoptosis-related ceRNA regulatory network was constructed, which included 24 long noncoding RNAs (lncRNAs), 41 microRNAs (miRNAs), and 4 messenger RNAs (mRNAs); the necroptosis-related ceRNA regulatory network included 16 lncRNAs, 20 miRNAs, and 6 mRNAs; and the pyroptosis-related ceRNA regulatory network included 15 lncRNAs, 18 miRNAs, and 6 mRNAs. Hub gene analysis identified hub nodes in each PCD-related ceRNA regulatory network and seven key regulatory axes in total, namely, lncRNA Malat1/miR-181a-5p/Mapt, lncRNA Malat1/miR-181b-5p/Mapt, lncRNA Neat1/miR-181a-5p/Mapt, and lncRNA Neat1/miR-181b-5p/Mapt for the apoptosis-related ceRNA regulatory network; lncRNA Neat1/miR-181a-5p/Tnf for the necroptosis-related ceRNA regulatory network; lncRNA Malat1/miR-181c-5p/Tnf for the pyroptosis-related ceRNA regulatory network; and lncRNAMalat1/miR-181a-5p for both necroptosis-related and pyroptosis-related ceRNA regulatory networks.Conclusion: The results of this study supported the hypothesis that these PCD pathways (apoptosis, necroptosis, pyroptosis, and PANoptosis) and crosstalk among them might be involved in ischemic stroke and that the key nodes and regulatory axes identified in this study might play vital roles in regulating the above processes. This may offer new insights into the potential mechanisms underlying cell death during cerebral I/R injury and provide new therapeutic targets for neuroprotection.

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“…Cochlear spiral ganglion progenitor cell-derived exosomes could protect cochleae damage from SCI/R through upregulating miR-181a-5p via inhibiting the inflammatory process [ 25 ]. Song et al revealed that miR-181a-5p was highly expressed in serum of acute I/R patients, mice, and OGD/R-induced N2a cells, which targeted En2 to block the Wnt pathway [ 37 ]. A study showed that miR-181a-5p alleviated neuronal injury in Parkinson’s disease cell model by inhibiting CXCL12 [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA H19 contributes to spinal cord ischemia/reperfusion injury through increasing neuronal pyroptosis by miR-181a-5p/HMGB1 axis

Guo

Wang

Alexander

et al. 2022

Aging

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Pyroptosis, a programmed inflammatory necrotizing cell death, is likely involved in spinal cord ischemia-reperfusion (SCI/R) injury, but the mechanisms initiating driving neuronal pyroptosis must be further revealed. The aim of this study is to unravel the mechanism of long non-coding RNA (lncRNA) H19 during SCI/R. SCI/R model was induced in C57BL/6 mice by blocking the aortic arch in vivo , and oxygen-glucose deprivation/reperfusion (OGD/R) injury model of PC12 cells was established in vitro . Our results showed that H19 and HMGB1 expression was upregulated, while miR-181a-5p was downregulated in the SCI/R mice and OGD/R-treated PC12 cells. SCI/R induced pathological damage, pyroptosis and inflammation compared with the sham group. H19 acted as a molecular sponge to suppress miR-181a-5p, and HMGB1 was identified as a direct target of miR-181a-5p. MiR-181a-5p overexpression inhibited the increase of IL-1β, IL-18 and TNF-α production and NLRP3, ASC, and Cleaved-caspase-1 expression in OGD/R-treated PC12 cells; while miR-181a-5p silencing exerted opposite effects. HMGB1 overexpression reversed H19 knockdown-mediated the inhibition of pyroptosis and inflammation in OGD/R-treated PC12 cells. In vivo , H19 knockdown promoted the hind limb motor function recovery and alleviated the pathological damage, pyroptosis and inflammation induced by SCI/R. LncRNA H19/miR-181a-5p/HMGB1 pathway contributes to pyroptosis via activating caspase1 signaling during SCI/R, suggesting that this axis may be a potent therapeutic target in SCI/R.

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Down-Regulation of miR-181a-5p Prevents Cerebral Ischemic Injury by Upregulating En2 and Activating Wnt/β-catenin Pathway

Cited by 12 publications

References 32 publications

Physiological Changes and Pathological Pain Associated with Sedentary Lifestyle-Induced Body Systems Fat Accumulation and Their Modulation by Physical Exercise

Physiological Changes and Pathological Pain Associated with Sedentary Lifestyle-Induced Body Systems Fat Accumulation and Their Modulation by Physical Exercise

Identification of programmed cell death-related gene signature and associated regulatory axis in cerebral ischemia/reperfusion injury

Long non-coding RNA H19 contributes to spinal cord ischemia/reperfusion injury through increasing neuronal pyroptosis by miR-181a-5p/HMGB1 axis

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