Novel circular RNAs expressed in brain microvascular endothelial cells after oxygen-glucose deprivation/recovery

Liu, Wei; Chen, Jia; Lu, Luo; Wang, Hailian; Min, Xiaoli; Xu, Jinzhi; Ma, Lei; Yang, Xiamin; Wang, Yingwei; Shang, Fei

doi:10.4103/1673-5374.262589

Cited by 21 publications

(4 citation statements)

References 43 publications

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“…The blood brain barrier is assembled by the ultrastructure of BMEC, and the cells connect with each other through the junction complex of tight junction and adhesion junction [ 43 ]. Liu w et al showed that in normal and oxygen glucose derived / recovered primary brain microvascular endothelial cells, 211 of the circRNAs were up-regulated and 326 were down regulated [ 44 ]. In addition, circRNAs have been shown to regulate a variety of biological functions of vascular endothelial cells, including proliferation, apoptosis, migration, angiogenesis and so on.…”

Section: Discussionmentioning

confidence: 99%

Up-regulation of circARF3 reduces blood-brain barrier damage in rat subarachnoid hemorrhage model via miR-31-5p/MyD88/NF-κB axis

Cai¹,

Xu³

et al. 2021

Aging

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Inflammation events have been found to aggravate brain injury and blood-brain barrier (BBB) damage following subarachnoid hemorrhage (SAH). This study probed the role and mechanism of a novel circRNA, circARF3, in regulating the BBB injury in SAH rats and hypoxia-induced vascular endothelial cell (VEC) injury in vitro . Levels of circARF3 and miR-31-5p were monitored by RT-PCR. The expression of inflammatory factors IL-1β and TNF-α was verified by ELISA. In vivo SAH model was constructed in Sprague Dawley (SD) rats. The BBB integrity and cerebral edema, as well as the neurological functions of the rats were evaluated. The apoptotic neurons and microglia in brain lesions were examined by immunohistochemistry (IHC). The MyD88/NF-κB pathway was tested by Western blot. Furthermore, gain-of functional assay were constructed to explore the effects of circARF3 and miR-31-5p in primary cultured brain microvascular endothelial cell (BMEC) injury and microglial inflammation induced by oxygen and glucose deprivation (OGD). circARF3 was significantly down-regulated in plasma and CSF in SAH patients with higher Fisher stages. In the SAH rat model, overexpressing circARF3 improved BBB integrity and neurological score, decreased neuronal apoptosis and microglial activation in ipsilateral basal cortex, with declined miR-31-5p expression and MyD88-NF-κB activation. In vitro , overexpressing circARF3 attenuated OGD-mediated integrity destruction of BMECs and microglial induced neuroinflammation, while overexpressing miR-31-5p had opposite effects. Mechanistically, circARF3 sponged miR-31-5p as an endogenous competitive RNA and dampens its expression, thus inactivating MyD88-NF-κB pathway. CircARF3 attenuates BBB destruction in SAH rats by regulating the miR-31-5p-activated MyD88-NF-κB pathway.

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Section: Discussionmentioning

confidence: 99%

Up-regulation of circARF3 reduces blood-brain barrier damage in rat subarachnoid hemorrhage model via miR-31-5p/MyD88/NF-κB axis

Cai¹,

Xu³

et al. 2021

Aging

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“…Blood-brain barrier selectively allows molecules to cross the barrier in order to protect the neonatal brains in physiological condition ( 84 ). Therefore, BBB damage is not only a consequence of but also a contributor to the progression of HI.…”

Section: Circrnas As Potential Biomarkers For Neurological Impairments and Diseasesmentioning

confidence: 99%

“…Modulation of circRNAs related to endothelial cell damage is beneficial to preserve the BBB integrity. For example, Liu et al suggested that circRNAs may regulate calcium ion and facilitate signal transduction so as to modulate the function of vascular endothelium avoid cell swelling, and lysis ( Figure 2C ) ( 84 ). So, BBB protection has been regarded as a potential therapeutic strategy for ischemic encephalopathy.…”

Section: Circrnas As Potential Biomarkers For Neurological Impairments and Diseasesmentioning

confidence: 99%

A Narrative Review of Circular RNAs in Brain Development and Diseases of Preterm Infants

Liu

et al. 2021

Front. Pediatr.

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Circular RNAs (circRNAs) generated by back-splicing are the vital class of non-coding RNAs (ncRNAs). Circular RNAs are highly abundant and stable in eukaryotes, and many of them are evolutionarily conserved. They are blessed with higher expression in mammalian brains and could take part in the regulation of physiological and pathophysiological processes. In addition, premature birth is important in neurodevelopmental diseases. Brain damage in preterm infants may represent the main cause of long-term neurodevelopmental disorders in surviving babies. Until recently, more and more researches have been evidenced that circRNAs are involved in the pathogenesis of encephalopathy of premature. We aim at explaining neuroinflammation promoting the brain damage. In this review, we summarize the current findings of circRNAs properties, expression, and functions, as well as their significances in the neurodevelopmental impairments, white matter damage (WMD) and hypoxic-ischemic encephalopathy (HIE). So we think that circRNAs have a direct impact on neurodevelopment and brain injury, and will be a powerful tool in the repair of the injured immature brain. Even though their exact roles and mechanisms of gene regulation remain elusive, circRNAs have potential applications as diagnostic biomarkers for brain damage and the target for neuroprotective intervention.

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“…Under adverse stimuli, the overreaction of vascular endothelial cells can damage the integrity of the BBB and aggravate injury. For example, the Px1 channel of vascular endothelial cells is activated and, therefore, releases ATP, inflammatory factors, and other signaling molecules to send “find-ME” signals to inflammatory cells after cerebral ischemic injury, thus attracting lymphocytes and aggravating inflammatory responses [ 4 , 5 ]. Therefore, endothelial cells play important roles in responding to external stimuli and maintaining the homeostasis of the brain, in which the secretion function is an important means whereby endothelial cells respond to stimuli.…”

Section: Introductionmentioning

confidence: 99%

LncRNA-Profile-Based Screening of Extracellular Vesicles Released from Brain Endothelial Cells after Oxygen–Glucose Deprivation

Zou²,

Liu³

et al. 2022

Brain Sciences

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Brain microvascular endothelial cells (BMECs) linked by tight junctions play important roles in cerebral ischemia. Intercellular signaling via extracellular vesicles (EVs) is an underappreciated mode of cell–cell crosstalk. This study aims to explore the potential function of long noncoding RNAs (lncRNAs) in BMECs’ secreted EVs. We subjected primary human and rat BMECs to oxygen and glucose deprivation (OGD). EVs were enriched for RNA sequencing. A comparison of the sequencing results revealed 146 upregulated lncRNAs and 331 downregulated lncRNAs in human cells and 1215 upregulated lncRNAs and 1200 downregulated lncRNAs in rat cells. Next, we analyzed the genes that were coexpressed with the differentially expressed (DE) lncRNAs on chromosomes and performed Gene Ontology (GO) and signaling pathway enrichment analyses. The results showed that the lncRNAs may play roles in apoptosis, the TNF signaling pathway, and leukocyte transendothelial migration. Next, three conserved lncRNAs between humans and rats were analyzed and confirmed using PCR. The binding proteins of these three lncRNAs in human astrocytes were identified via RNA pulldown and mass spectrometry. These proteins could regulate mRNA stability and translation. Additionally, the lentivirus was used to upregulate them in human microglial HMC3 cells. The results showed NR_002323.2 induced microglial M1 activation. Therefore, these results suggest that BMECs’ EVs carry the lncRNAs, which may regulate gliocyte function after cerebral ischemia.

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Novel circular RNAs expressed in brain microvascular endothelial cells after oxygen-glucose deprivation/recovery

Cited by 21 publications

References 43 publications

Up-regulation of circARF3 reduces blood-brain barrier damage in rat subarachnoid hemorrhage model via miR-31-5p/MyD88/NF-κB axis

Up-regulation of circARF3 reduces blood-brain barrier damage in rat subarachnoid hemorrhage model via miR-31-5p/MyD88/NF-κB axis

A Narrative Review of Circular RNAs in Brain Development and Diseases of Preterm Infants

LncRNA-Profile-Based Screening of Extracellular Vesicles Released from Brain Endothelial Cells after Oxygen–Glucose Deprivation

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