Alteration in Abundance and Compartmentalization of Inflammation-Related miRNAs in Plasma After Intracerebral Hemorrhage

Guo, Dong; Liu, Junni; Wang, Weihua; Fang, Hao; Sun, Xuedong; Wu, Xiao; Bu, Peili; Zhang, Yun; Liu, Yu; Liu, Fengqing; Zhang, Qunye; Jiang, Fan

doi:10.1161/strokeaha.111.000835

Cited by 56 publications

(56 citation statements)

References 15 publications

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“…[30][31][32][33] Abnormal expression of miRNAs appears to be a common feature of many human diseases, ranging from cardiovascular disorders to cancer [30][31][32][33] and most recently inflammatory diseases. 9,34,35 Here, we present evidence showing that overexpression of the GSK3β inhibitor-dependent miRNAs, miR-98 and let-7g*, can decrease leukocyte adhesion to and migration across the BBB, in both in vitro and in vivo models. Not all miRNAs had similar abilities to improve BBB function in an in vitro model.…”

Section: Discussionmentioning

confidence: 85%

miR-98 and let-7g* Protect the Blood-Brain Barrier Under Neuroinflammatory Conditions

Rom

Dykstra

Zuluaga-Ramirez

et al. 2015

J Cereb Blood Flow Metab

105

110

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Pathologic conditions in the central nervous system, regardless of the underlying injury mechanism, show a certain level of blood-brain barrier (BBB) impairment. Endothelial dysfunction is the earliest event in the initiation of vascular damage caused by inflammation due to stroke, atherosclerosis, trauma, or brain infections. Recently, microRNAs (miRNAs) have emerged as a class of gene expression regulators. The relationship between neuroinflammation and miRNA expression in brain endothelium remains unexplored. Previously, we showed the BBB-protective and anti-inflammatory effects of glycogen synthase kinase (GSK) 3β inhibition in brain endothelium in in vitro and in vivo models of neuroinflammation. Using microarray screening, we identified miRNAs induced in primary human brain microvascular endothelial cells after exposure to the pro-inflammatory cytokine, tumor necrosis factor-α, with/out GSK3β inhibition. Among the highly modified miRNAs, let-7 and miR-98 were predicted to target the inflammatory molecules, CCL2 and CCL5. Overexpression of let-7 and miR-98 in vitro and in vivo resulted in reduced leukocyte adhesion to and migration across endothelium, diminished expression of pro-inflammatory cytokines, and increased BBB tightness, attenuating barrier 'leakiness' in neuroinflammation conditions. For the first time, we showed that miRNAs could be used as a therapeutic tool to prevent the BBB dysfunction in neuroinflammation.

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Section: Discussionmentioning

confidence: 85%

miR-98 and let-7g* Protect the Blood-Brain Barrier Under Neuroinflammatory Conditions

Rom

Dykstra

Zuluaga-Ramirez

et al. 2015

J Cereb Blood Flow Metab

105

110

View full text Add to dashboard Cite

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“…Inflammationrelated miR-27a-3p levels were significantly increased in SC and plasma of EAE mice at the peak of the disease. Previously miR-27a levels were shown to increase significantly in the plasma of stroke patients, and bioinformatics analysis linked the expression with inflammation-related events (Guo et al 2013). miR-126 is increased in MS patients during relapse and patients on interferon beta (IFN-β) therapy have reduced plasma levels of miR-126 (Meira et al 2014).…”

Section: Discussionmentioning

confidence: 99%

Targeted Stage-Specific Inflammatory microRNA Profiling in Urine During Disease Progression in Experimental Autoimmune Encephalomyelitis: Markers of Disease Progression and Drug Response

Singh

Deshpande

Salehiniya

et al. 2015

J Neuroimmune Pharmacol

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Recently, microRNAs (miRNAs) have been implicated in regulating neuroinflammatory and demyelinative responses in multiple sclerosis (MS) and its mouse model of experimental autoimmune encephalomyelitis (EAE). miRNAs have also been studied as biomarkers of disease pathology and drug-response in MS. However, no complete miRNA profiling at various stages of EAE disease has been examined, especially in the urine. We carried out a systematic analysis of miRNAs in the urine exosomes as well as in the plasma and spinal cord at pre-onset, onset and peak stages of EAE established in the chronic B6 mice model. For the first time, we provide evidence that urine exosomes can be a specific and sensitive source of miRNA biomarkers for all 3 stages of EAE disease. In a significant observation, we observed that miR-155-5p expression increased in urine exosomes, plasma and spinal cord 6 days before the onset of disease, suggesting its early involvement in the pathology of EAE disease. We also analyzed the effect of Glatiramer acetate (GA; copaxone) treatment, an approved treatment for MS patients, in modulating miRNA expression at the peak of EAE disease. We identified miR-155-5p, miR-27a-3p, miR-9-5p and miR-350-5p as putative GA-treatment responsive miRNA biomarkers. Since, EAE is a mainly CD4 cells mediated disease, we also examined the above set of miRNAs and found to be significantly altered in T cells polarized to Th1 and Th17 phenotype, similar to urine exosomes. Thus, urine exosome miRNAs hold the potential to be defined as novel accessible stage-specific biomarkers of EAE (MS) disease as well as treatment response.

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“…Leung et al (2014) showed that miR-124-3p levels were significantly higher while miR-16 levels were significantly lower in the plasma from hemorrhagic stroke patients compared to ischemic stroke patients indicating that blood miRNA profiles can predict the stroke subtypes in humans as well. A set of 30 inflammation-related miRNAs including miR-494, miR-1471 and miR-874 (upregulated) and miR-301a, miR-144 and miR-122 (downregulated) were observed to be significantly altered in plasma microvesicles after ICH in both male and female patients (Guo et al, 2013). Hematoma formation after ICH can be identified by miRNA profiling.…”

Section: Micrornas As Stroke Biomarkersmentioning

confidence: 99%

Non-coding RNAs and neuroprotection after acute CNS injuries

Chandran

Mehta

2017

Neurochemistry International

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Accumulating evidence indicates that various classes of non-coding RNAs (ncRNAs) including microRNAs (miRNAs), PIWI-interacting RNAs (piRNAs) and long non-coding RNAs (lncRNAs) play important roles in normal state as well as the diseases of the CNS. Interestingly, ncRNAs have been shown to interact with messenger RNA, DNA and proteins, and these interactions could induce epigenetic modifications and control transcription and translation, thereby adding a new layer of genomic regulation. The ncRNA expression profiles are known to be altered after acute CNS injuries including stroke, traumatic brain injury and spinal cord injury that are major contributors of morbidity and mortality worldwide. Hence, a better understanding of the functional significance of ncRNAs following CNS injuries could help in developing potential therapeutic strategies to minimize the neuronal damage in those conditions. The potential of ncRNAs in blood and CSF as biomarkers for diagnosis and/or prognosis of acute CNS injuries has also gained importance in the recent years. This review highlighted the current progress in the understanding of the role of ncRNAs in initiation and progression of secondary neuronal damage and their application as biomarkers after acute CNS injuries.

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Alteration in Abundance and Compartmentalization of Inflammation-Related miRNAs in Plasma After Intracerebral Hemorrhage

Cited by 56 publications

References 15 publications

miR-98 and let-7g* Protect the Blood-Brain Barrier Under Neuroinflammatory Conditions

miR-98 and let-7g* Protect the Blood-Brain Barrier Under Neuroinflammatory Conditions

Targeted Stage-Specific Inflammatory microRNA Profiling in Urine During Disease Progression in Experimental Autoimmune Encephalomyelitis: Markers of Disease Progression and Drug Response

Non-coding RNAs and neuroprotection after acute CNS injuries

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