Long non-coding RNA MEG3 promotes cerebral ischemia-reperfusion injury through increasing pyroptosis by targeting miR-485/AIM2 axis

Liang, Ji; Wang, Qiang; Li, Junqi; Guo, Ting; Yu, Dan

doi:10.1016/j.expneurol.2019.113139

Cited by 147 publications

(86 citation statements)

References 37 publications

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“…Furthermore, it has been shown that the cyclic GMP-AMP synthase antagonist A151 effectively reduced the expression of AIM2 and its downstream cascade, thereby significantly reducing neuro-deficits and diminished cell death [ 29 ]. Moreover, Liang and colleagues have indicated AIM2 as a direct target of miR-485 and postulated that the long non-coding RNA MEG3 promotes cerebral ischemia-reperfusion injury by increasing pyroptosis by targeting the miR-485/AIM2 axis [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Gonadal Hormones E2 and P Mitigate Cerebral Ischemia-Induced Upregulation of the AIM2 and NLRC4 Inflammasomes in Rats

Habib

Harms

Zendedel

et al. 2020

IJMS

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Acute ischemic stroke (AIS) is a devastating neurological condition with a lack of neuroprotective therapeutic options, despite the reperfusion modalities thrombolysis and thrombectomy. Post-ischemic brain damage is aggravated by an excessive inflammatory cascade involving the activation and regulation of the pro-inflammatory cytokines IL-1β and IL-18 by inflammasomes. However, the role of AIM2 and NLRC4 inflammasomes and the influence of the neuroprotective steroids 17β-estradiol (E2) and progesterone (P) on their regulation after ischemic stroke have not yet been conclusively elucidated. To address the latter, we subjected a total of 65 rats to 1 h of transient Middle Cerebral Artery occlusion (tMCAO) followed by a reperfusion period of 72 h. Moreover, we evaluated the expression and regulation of AIM2 and NLRC4 in glial single-cell cultures (astroglia and microglia) after oxygen–glucose deprivation (OGD). The administration of E2 and P decreased both infarct sizes and neurological impairments after cerebral ischemia in rats. We detected a time-dependent elevation of gene and protein levels (Western Blot/immunohistochemistry) of the AIM2 and NLRC4 inflammasomes in the post-ischemic brains. E2 or P selectively mitigated the stroke-induced increase of AIM2 and NLRC4. While both inflammasomes seemed to be exclusively abundant in neurons under physiological and ischemic conditions in vivo, single-cell cultures of cortical astrocytes and microglia equally expressed both inflammasomes. In line with the in vivo data, E and P selectively reduced AIM2 and NLRC4 in primary cortical astrocytes and microglial cells after OGD. In conclusion, the post-ischemic elevation of AIM2 and NLRC4 and their down-regulation by E2 and P may shed more light on the anti-inflammatory effects of both gonadal hormones after stroke.

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Section: Discussionmentioning

confidence: 99%

Gonadal Hormones E2 and P Mitigate Cerebral Ischemia-Induced Upregulation of the AIM2 and NLRC4 Inflammasomes in Rats

Habib

Harms

Zendedel

et al. 2020

IJMS

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“…Inflammasome could contribute to ischemic brain injury by inducing inflammation and pyroptosis. LncRNA maternally expressed gene 3 (MEG3) triggers caspase1/GSDMD-mediated pyroptosis through inflammasome absent in melanoma 2 (AIM2) to promote cerebral ischemia-reperfusion injury and induce ischemic stroke in an oxygen-glucose deprivation/reperfusion-treated neurocytes model and in a middle cerebral artery occlusion rat model [69]. Pyroptosis-induced inflammation is involved in the development of human inflammatory diseases.…”

Section: Non-coding Rna-regulated Pyroptosis Impacts On Inflammatory mentioning

confidence: 99%

Mechanisms and Therapeutic Regulation of Pyroptosis in Inflammatory Diseases and Cancer

Zheng

2020

IJMS

146

111

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Programmed Cell Death (PCD) is considered to be a pathological form of cell death when mediated by an intracellular program and it balances cell death with survival of normal cells. Pyroptosis, a type of PCD, is induced by the inflammatory caspase cleavage of gasdermin D (GSDMD) and apoptotic caspase cleavage of gasdermin E (GSDME). This review aims to summarize the latest molecular mechanisms about pyroptosis mediated by pore-forming GSDMD and GSDME proteins that permeabilize plasma and mitochondrial membrane activating pyroptosis and apoptosis. We also discuss the potentiality of pyroptosis as a therapeutic target in human diseases. Blockade of pyroptosis by compounds can treat inflammatory disease and pyroptosis activation contributes to cancer therapy.

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“…81 The AIM2 inflammasome also plays detrimental roles in several types of brain injury such as ischemic brain injury, cerebral ischemic reperfusion injury, subarachnoid hemorrhagia, and traumatic brain injury. [82][83][84][85] Additional inflammatory roles of AIM2 have been reported in vascular diseases such as atherosclerosis and cardiomyopathy. 86 Atherosclerosis-prone ApoE -/mice fed a high-fat diet showed enhanced expression of AIM2 in vascular smooth muscle cells (VSMCs), which correlated with high ICAM-1 expression in these cells.…”

Section: Autoimmune and Sterile Inflammatory Diseasesmentioning

confidence: 97%

AIM2 in health and disease: Inflammasome and beyond

Kumari

Russo

Shivcharan

et al. 2020

Immunological Reviews

155

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Nucleic acid sensing is a critical mechanism by which the immune system monitors for pathogen invasion. A set of germline‐encoded innate immune receptors detect microbial DNA in various compartments of the cell, such as endosomes, the cytosol, and the nucleus. Sensing of microbial DNA through these receptors stimulates, in most cases, interferon regulatory factor‐dependent type I IFN synthesis followed by JAK/STAT‐dependent interferon‐stimulated gene expression. In contrast, the detection of DNA in the cytosol by AIM2 assembles a macromolecular complex called the inflammasome, which unleashes the proteolytic activity of a cysteine protease caspase‐1. Caspase‐1 cleaves and activates the pro‐inflammatory cytokines such as IL‐1β and IL‐18 and a pore‐forming protein, gasdermin D, which triggers pyroptosis, an inflammatory form of cell death. Research over the past decade has revealed that AIM2 plays essential roles not only in host defense against pathogens but also in inflammatory diseases, autoimmunity, and cancer in inflammasome‐dependent and inflammasome‐independent manners. This review discusses the latest advancements in our understanding of AIM2 biology and its functions in health and disease.

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Long non-coding RNA MEG3 promotes cerebral ischemia-reperfusion injury through increasing pyroptosis by targeting miR-485/AIM2 axis

Cited by 147 publications

References 37 publications

Gonadal Hormones E2 and P Mitigate Cerebral Ischemia-Induced Upregulation of the AIM2 and NLRC4 Inflammasomes in Rats

Gonadal Hormones E2 and P Mitigate Cerebral Ischemia-Induced Upregulation of the AIM2 and NLRC4 Inflammasomes in Rats

Mechanisms and Therapeutic Regulation of Pyroptosis in Inflammatory Diseases and Cancer

AIM2 in health and disease: Inflammasome and beyond

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