MicroRNA-126-3p attenuates blood-brain barrier disruption, cerebral edema and neuronal injury following intracerebral hemorrhage by regulating PIK3R2 and Akt

Xi, Tianyang; Jin, Feng; Zhu, Ying; Wang, Jialu; Tang, Ling; Wang, Yanzhe; Liebeskind, David S; He, Zhiwei

doi:10.1016/j.bbrc.2017.10.064

Cited by 77 publications

(63 citation statements)

References 34 publications

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“…However, overexpression of miR‐126p enhanced laser‐induced choroidal neovascularization. In addition to the VEGFA control, miR‐126‐3p down‐regulation is associated with increased inflammation, epithelial‐mesenchymal transition (EMT), regulatory proteins expression and cellular proliferation . Therefore, miR‐126‐3p may be an important epigenetic regulator in the development of wet AMD.…”

Section: Discussionmentioning

confidence: 99%

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Expression of VEGFA‐regulating miRNAs and mortality in wet AMD

Błasiak

Watała

Tuuminen

et al. 2019

J Cellular Molecular Medi

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MicroRNAs (miRNAs) regulate gene expression; many of them act in the retinal pigment epithelium (RPE), and RPE degeneration is known to be a critical factor in age‐related macular degeneration (AMD). Repeated injections with anti‐VEGFA (vascular endothelial growth factor A) are the only effective therapy in wet AMD. We investigated the correlation between the expression of 18 miRNAs involved in the regulation of the VEGFA gene in serum of 76 wet AMD patients and 70 controls. Efficacy of anti‐VEGFA treatment was evaluated by counting the number of injections delivered up to 12 years. In addition, we compared the relative numbers of deaths in patient with AMD and control groups. We observed a decreased expression of miR‐34‐5p, miR‐126‐3p, miR‐145‐5p and miR‐205‐5p in wet AMD patients as compared with controls. These miRNAs are involved in the regulation of angiogenesis, cytoprotection and protein clearance. No miRNA was significantly correlated with the treatment outcome. Wet AMD patients had greater mortality than controls, and their survival was inversely associated with the number of anti‐VEGFA injections per year. No association was observed between miRNA expression and mortality. Our study emphasizes the need to clarify the role of miRNA regulation in AMD pathogenesis.

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Section: Discussionmentioning

confidence: 99%

“…30 cellular proliferation. [35][36][37][38] Therefore, miR-126-3p may be an important epigenetic regulator in the development of wet AMD. miR-145-5p is known to be a negative regulator of angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Expression of VEGFA‐regulating miRNAs and mortality in wet AMD

Błasiak

Watała

Tuuminen

et al. 2019

J Cellular Molecular Medi

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“…Adult male Sprague-Dawley rats (weighing 250 -280 g) were randomly assigned to four groups. ICH was induced by collagenase according to a method described previously (38,39). Briefly, the rats were anesthetized with 50 mg/kg sodium pentobarbital via intraperitoneal injection and fixed in a stereotaxic frame in a prone position.…”

Section: Establishment Of the Ich Model And Administration Of The Mirmentioning

confidence: 99%

miR-27a-3p protects against blood–brain barrier disruption and brain injury after intracerebral hemorrhage by targeting endothelial aquaporin-11

Jin

Zhu

et al. 2018

Journal of Biological Chemistry

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Previous studies have reported that miR-27a-3p is down-regulated in the serum of patients with intracerebral hemorrhage (ICH), but the implication of miR-27a-3p down-regulation in post-ICH complications remains elusive. Here we verified miR-27a-3p levels in the serum of ICH patients by real-time PCR and observed that miR-27a-3p is also significantly reduced in the serum of these patients. We then further investigated the effect of miR-27a-3p on post-ICH complications by intraventricular administration of a miR-27a-3p mimic in rats with collagenaseinduced ICH. We found that the hemorrhage markedly reduced miR-27a-3p levels in the hematoma, perihematomal tissue, and serum and that intracerebroventricular administration of the miR-27a-3p mimic alleviated behavioral deficits 24 h after ICH. Moreover, ICH-induced brain edema, vascular leakage, and leukocyte infiltration were also attenuated by this mimic. Of note, miR-27a-3p mimic treatment also inhibited neuronal apoptosis and microglia activation in the perihematomal zone. We further observed that the miR-27a-3p mimic suppressed the up-regulation of aquaporin-11 (AQP11) in the perihematomal area and in rat brain microvascular endothelial cells (BMECs). Moreover, miR-27a-3p down-regulation increased BMEC monolayer permeability and impaired BMEC proliferation and migration. In conclusion, miR-27a-3p down-regulation contributes to brain edema, blood-brain barrier disruption, neuron loss, and neurological deficits following ICH. We conclude that application of exogenous miR-27a-3p may protect against post-ICH complications by targeting AQP11 in the capillary endothelial cells of the brain. This study was supported by a grant from the National Natural Science Foundation of China (81271291). The authors declare that they have no conflicts of interest with the contents of this article. This article contains Fig. S1.

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“…Recent evidence has shown that microRNAs (miRNAs), small endogenous RNAs of 21-25 nucleotides capable of guiding the posttranscriptional silencing of their target mRNAs through base pairing encompassing mature mRNA 3′-untranslated region (3′-UTR), play essential regulatory roles in the development of BTI [4][5][6]. For instance, miR-126 is implicated in brain vascular inflammation and intracerebroventricular (I.C.V) administration of miR-126-3p mimic can significantly suppress the upregulation of phosphoinositide-3-kinase regulatory subunit 2, as well as reduce blood-brain barrier permeability and brain edema [7]. Moreover, Peli1 is an important E3 ubiquitin-protein ligase contributing to neuroinflammation.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-7, synergizes with RORα, negatively controls the pathology of brain tissue inflammation

Yue

Zhao

Chen

et al. 2020

J Neuroinflammation

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Background: Accumulating evidence has documented that microRNA-7 (miR-7) plays an important role in the pathology of various diseases. However, the potential role of miR-7 in brain tissue inflammation (BTI) remains unclear. Methods: We detected the expression of miR-7 in LPS-induced murine BTI model and observed the possible effects of miR-7 deficiency on the pathology of BTI. To elucidate the mechanism, the target gene of miR-7 was screened out by Gene chip assay and its potential roles in BTI were evaluated by Western blot, immunofluorescence, and RNAi assay, respectively.Results: MiR-7 was upregulated in brain tissue in BTI mice and its deficiency could significantly aggravate the pathology of brain tissue. Moreover, RORα, a new target molecule of miR-7, was upregulated in brain tissue from miR-7 deficiency BTI mice. Of note, downregulation of RORα could remarkably exacerbate the pathology of brain tissue and elevate the transduction of NF-κB and ERK1/2 signaling pathways in brain tissue from miR-7 deficiency BTI mice. Furthermore, RORα and miR-7 were dominantly co-expressed in neurons of BTI mice. Finally, RORα synergized with miR-7 to control the inflammatory reaction of neuronal cells in response to LPS stimulation.Conclusions: MiR-7 expression is upregulated in BTI model. Moreover, miR-7 synergizes with its target gene RORα to control the inflammation reaction of neurons, thereby orchestrating the pathology of BTI.

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MicroRNA-126-3p attenuates blood-brain barrier disruption, cerebral edema and neuronal injury following intracerebral hemorrhage by regulating PIK3R2 and Akt

Cited by 77 publications

References 34 publications

Expression of VEGFA‐regulating miRNAs and mortality in wet AMD

Expression of VEGFA‐regulating miRNAs and mortality in wet AMD

miR-27a-3p protects against blood–brain barrier disruption and brain injury after intracerebral hemorrhage by targeting endothelial aquaporin-11

MicroRNA-7, synergizes with RORα, negatively controls the pathology of brain tissue inflammation

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