ASK1 modulates the expression of microRNA Let7A in microglia under high glucose in vitro condition

Song, Jeong Sup; Lee, Jong Eun

doi:10.3389/fncel.2015.00198

Cited by 24 publications

(21 citation statements)

References 111 publications

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“…The ASK1/p38 signaling pathway via TLRs is critical for chemokine production and promotes inflammation and neurotoxicity after multiple sclerosis ( Guo et al, 2010 ). In line with studies that have demonstrated that ASK1 inhibition attenuates pro-inflammatory cytokines in microglia, ASK1 was found to be associated with TNF-α and iNOS production in primary microglial cell culture, and M1 macrophage suppression by a Class A scavenger receptor resulted in reductions of IL-6, IL-1β, and TNF-α, decreasing ASK1/p38/NF-κB pathway signaling, under pathologic conditions ( Hu et al, 2011 ; Katome et al, 2013 ; Song and Lee, 2015 ). Previous reports have shown that inhibition of ASK1 reduces M1 phenotype after injury and ASK1 also played a role in our results.…”

Section: Discussionsupporting

confidence: 81%

Regulation of Microglia and Macrophage Polarization via Apoptosis Signal-Regulating Kinase 1 Silencing after Ischemic/Hypoxic Injury

Cheon

Kim

et al. 2017

Front. Mol. Neurosci.

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Inflammation is implicated in ischemic stroke and is involved in abnormal homeostasis. Activation of the immune system leads to breakdown of the blood–brain barrier and, thereby, infiltration of immune cells into the brain. Upon cerebral ischemia, infiltrated macrophages and microglia (resident CNS immune cell) are activated, change their phenotype to M1 or M2 based on the microenvironment, migrate toward damaged tissue, and are involved in repair or damage. Those of M1 phenotype release pro-inflammatory mediators, which are associated with tissue damage, while those of M2 phenotype release anti-inflammatory mediators, which are related to tissue recovery. Moreover, late inflammation continually stimulates immune cell infiltration and leads to brain infarction. Therefore, regulation of M1/M2 phenotypes under persistent inflammatory conditions after cerebral ischemia is important for brain repair. Herein, we focus on apoptosis signal-regulating kinase 1 (ASK1), which is involved in apoptotic cell death, brain infarction, and production of inflammatory mediators after cerebral ischemia. We hypothesized that ASK1 is involved in the polarization of M1/M2 phenotype and the function of microglia and macrophage during the late stage of ischemia/hypoxia. We investigated the effects of ASK1 in mice subjected to middle cerebral artery occlusion and on BV2 microglia and RAW264.7 macrophage cell lines subjected to oxygen-glucose deprivation. Our results showed that ASK1 silencing effectively reduced Iba-1 or CD11b-positive cells in ischemic areas, suppressed pro-inflammatory cytokines, and increased anti-inflammatory mediator levels at 7 days after cerebral ischemia. In cultured microglia and macrophages, ASK1 inhibition, induced by NQDI-1 drug, decreased the expression and release of M1-associated factors and increased those of M2-associated factors after hypoxia/reperfusion (H/R). At the gene level, ASK1 inhibition suppressed M1-associated genes and augmented M2-associated genes. In gap closure assay, ASK1 inhibition reduced the migration rate of microglia and macrophages after H/R. Taken together, our results provide new information that suggests ASK1 controls the polarization of M1/M2 and the function of microglia and macrophage under sustained-inflammatory conditions. Regulation of persistent inflammation via M1/M2 polarization by ASK1 is a novel strategy for repair after ischemic stroke.

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Section: Discussionsupporting

confidence: 81%

Regulation of Microglia and Macrophage Polarization via Apoptosis Signal-Regulating Kinase 1 Silencing after Ischemic/Hypoxic Injury

Cheon

Kim

et al. 2017

Front. Mol. Neurosci.

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“…In the studies on let-7a in LPS-treated microglial BV2 cells, let-7a level is found to be remarkably decreased; however, let-7a overexpression can reduce the production of inducible nitric oxide synthase (iNOS) and IL-6, while promoting anti-inflammatory genes at the same time in microglia (68). Consistent with this finding, let-7a can strongly inhibit the expression of inflammatory cytokines by controlling the activation of apoptosis signal-regulating kinase 1 (ASK1), thus activating anti-inflammatory cytokines such as IL-10 and Mycs in microglia (69). Meanwhile, let-7 could act as a regulator of microglial function during inflammation and be a novel target for enhancing the beneficial function of microglia in CNS disorders.…”

Section: The Modulation Role Of Neuroinflammation In Admentioning

confidence: 65%

The Regulation of microRNAs in Alzheimer's Disease

Kou

Chen

2020

Front. Neurol.

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MicroRNAs are small non-coding nucleic acids that are responsible for regulating the gene expression by binding to the coding region and 3' and 5' un-translated region of target messenger RNA. Approximately 70% of known microRNAs are expressed in the brain and increasing evidences demonstrate the possible involvement of microRNAs in Alzheimer's disease (AD) according to the statistics. The characteristic symptoms of AD are the progressive loss of memory and cognitive functions due to the deposition of amyloid β (Aβ) peptide, intracellular aggregation of hyperphosphorylated Tau protein, the loss of synapses, and neuroinflammation, as well as dysfunctional autophagy. Therefore, microRNA-mediated regulation for above-mentioned changes may be the potential therapeutic strategies for AD. In this review, the role of specific microRNAs involved in AD and corresponding applications are systematically discussed, including positive effects associated with the reduction of Aβ or Tau protein, the protection of synapses, the inhibition of neuroinflammation, the mitigation of aging, and the induction of autophagy in AD. It will be beneficial to develop effective targets for establishing a cross link between pharmacological intervention and AD in the near future.

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“…Many studies have identified specific miRNAs expression profiles of diabetes and described the critical roles of miRNAs in insulin secretion [ 21 , 22 ], pancreatic development and function [ 22 ] and diabetic cardiovascular complications [ 23 ]. However, the role of several miRNAs, such as miR-21, -146a [ 24 , 25 ] and let7A [ 26 ] as regulators in inflammation and oxidative stresses has been reported.…”

Section: Discussionmentioning

confidence: 99%

Oscillating glucose induces microRNA-185 and impairs an efficient antioxidant response in human endothelial cells

Sala

Cattaneo

Nigris

et al. 2016

Cardiovasc Diabetol

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BackgroundIntracellular antioxidant response to high glucose is mediated by Cu/Mn-superoxide dismutases (SOD-1/SOD-2), catalase (CAT) and glutathione peroxidases (GPx), particularly glutathione peroxidase-1 (GPx-1). Although oscillating glucose can induce a more deleterious effect than high glucose on endothelial cells, the mechanism by which oscillating glucose exerts its dangerous effects is incompletely understood; however, the involvement of oxidative damage has been generally accepted. In this study we sought to determine whether oscillating glucose differentially modulates antioxidant response, and to elucidate the potential regulatory mechanisms exerted by the microRNA-185 (miR-185).MethodsHuman endothelial cells were exposed for 1 week to constant and oscillating high glucose. SOD-1, SOD-2, CAT and GPx-1, as well as two markers of oxidative stress [8-hydroxy-2′-deoxyguanosine (8-OHdG) and the phosphorylated form of H2AX (γ-H2AX)] were measured at the end of the experiment. Intracellular miR-185 was measured and loss-of function assays were performed in HUVEC. Bioinformatic tool was used to predict the link between miR-185 on 3′UTR of GPx-1 gene. Luciferase assay was performed to confirm the binding on HUVEC.ResultsAfter exposure to constant high glucose SOD-1 and GPx-1 increased, while in oscillating glucose SOD-1 increased and GPx-1 did not. SOD-2 and CAT remained unchanged under both conditions. A critical involvement of oscillating glucose-induced miR-185 in the dysregulation of endogenous GPx-1 was found. Computational analyses predict GPx-1 as miR-185′s target. HUVEC cultures were used to confirm glucose’s causal role on the expression of miR-185, its target mRNA and protein and finally the activation of antioxidant response. In vitro luciferase assays confirmed computational predictions targeting of miR-185 on 3′-UTR of GPx-1 mRNA. Knockdown of miR-185, using anti-miR-185 inhibitor, was accompanied by a significant upregulation of GPx-1 in oscillating glucose. 8-OHdG and γ-H2AX increased more in oscillating glucose than in constant high glucose.ConclusionsGlucose oscillations may exert more deleterious effects on the endothelium than high glucose, likely due to an impaired response of GPx-1, coupled by the upregulation of miR-185.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-016-0390-9) contains supplementary material, which is available to authorized users.

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ASK1 modulates the expression of microRNA Let7A in microglia under high glucose in vitro condition

Cited by 24 publications

References 111 publications

Regulation of Microglia and Macrophage Polarization via Apoptosis Signal-Regulating Kinase 1 Silencing after Ischemic/Hypoxic Injury

Regulation of Microglia and Macrophage Polarization via Apoptosis Signal-Regulating Kinase 1 Silencing after Ischemic/Hypoxic Injury

The Regulation of microRNAs in Alzheimer's Disease

Oscillating glucose induces microRNA-185 and impairs an efficient antioxidant response in human endothelial cells

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