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

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

doi:10.1074/jbc.ra118.001858

Cited by 95 publications

(79 citation statements)

References 40 publications

(38 reference statements)

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“…In this respect, although most of the knowledge concerning the role of AQP1 and AQP4 on the CSF homeostasis has been obtained in animal models, during recent years, growing studies indicate that these AQPs might have similar functions in humans, and their alterations would been implicated in different pathophysiological conditions [7,15,42,43]. Moreover, in the last years, another AQP, AQP11, has been reported to be expressed in the brain [44,45]. Further experimental work should be performed to address if some of the modifications observed in the double-AQP −/− KO could be related with compensation of other AQPs and/or alterations in the brain water content.…”

Section: Discussionmentioning

confidence: 99%

AQP1 and AQP4 Contribution to Cerebrospinal Fluid Homeostasis

Trillo-Contreras

Toledo‐Aral

Echevarría

et al. 2019

Cells

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Aquaporin 1 (AQP1), expressed in epithelial cells of the choroid plexus, and aquaporin 4 (AQP4) present in ependymal cells and glia limitants have been proposed to play a significant role in cerebrospinal fluid (CSF) production and homeostasis. However, the specific contribution of each water channel to these functions remains unknown, being a subject of debate during the last years. Here, we analyzed in detail how AQP1 and AQP4 participate in different aspects of the CSF homeostasis such as the load and drainage of ventricles, and further explored if these proteins play a role in the ventricular compliance. To do that, we carried out records of intraventricular pressure and CSF outflow, and evaluated ventricular volume by magnetic resonance imaging in AQP1−/−, AQP4−/−, double AQP1−/−-AQP4−/− knock out and wild type mice controls. The analysis performed clearly showed that both AQPs have a significant participation in the CSF production, and additionally revealed that the double AQP1-AQP4 mutation alters the CSF drainage and the ventricular compliance. The data reported here indicate a significant extra-choroidal CSF formation mediated by AQP4, supporting the idea of an important and constant CSF production/absorption process, sustained by efflux/influx of water between brain capillaries and interstitial fluid. Moreover, our results suggest the participation of AQPs in structural functions also related with CSF homeostasis such as the distensibility capacity of the ventricular system.

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Section: Discussionmentioning

confidence: 99%

AQP1 and AQP4 Contribution to Cerebrospinal Fluid Homeostasis

Trillo-Contreras

Toledo‐Aral

Echevarría

et al. 2019

Cells

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“…Previous studies demonstrated that these candidate miRNAs could facilitate neuron survival by regulating expression of genes that have induction of transcription in response to injury. For example, MiR-27a-3p can protect against blood-brain barrier disruption and brain injury by modulating expression of endothelial aquaporin-11 18 . Meanwhile microRNA-27a can suppress expression of the Apaf-1 protein to mitigate hypoxia-induced neuronal apoptosis 19 .…”

Section: Discussionmentioning

confidence: 99%

Circ-camk4 involved in cerebral ischemia/reperfusion induced neuronal injury

Zhang

Wang

et al. 2020

Sci Rep

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Stroke and subsequent cerebral ischemia/reperfusion (I/R) injury is a frequently occurring disease that can have serious consequences in the absence of timely intervention. Circular RNAs (circRNAs) in association with microRNAs (miRNAs) and RNA-binding proteins (RBPs) can influence gene expression. However, whether circRNAs have a role in cerebral I/R injury pathogenesis, especially soon after onset, is unclear. In this study, we used the SD rat middle cerebral artery occlusion (MCAO) model of stroke to examine the role of circRNAs in cerebral I/R injury. We used high-throughput sequencing (HTS) to compare the expression levels of circRNAs in cerebral cortex tissue from MCAO rats during the occlusion-reperfusion latency period 3 hours after I/R injury with those in control cerebral cortices. Our sequencing results revealed that expression levels of 44 circRNAs were significantly altered after I/R, with 16 and 28 circRNAs showing significant up-and down-regulation, respectively, relative to levels in control cortex. We extended these results in vitro in primary cultured neuron cells exposed to oxygen-glucose deprivation/reperfusion (OGD/R) using qRT-PCR to show that levels of circ-camk4 were increased in OGD/R neurons relative to control neurons. Bioinformatics analyses predicted that several miRNAs could be associated with circ-camk4 and this prediction was confirmed in a RNA pull-down assay. KEGG analysis to predict pathways that involve circ-camk4 included the glutamatergic synapse pathway, MAPK signaling pathway, and apoptosis signaling pathways, all of which are known to be involved in brain injury after I/R. Our results also demonstrate that levels of the human homolog to circ-camk4 (hsa-circ-camk4) are elevated in SH-SY5Y cells exposed to OGD/R treatment. Overexpression of hsa-circ-camk4 in SH-SY5Y cells significantly increased the rate of cell death after OGD/R, suggesting that circ-camk4 may play a key role in progression of cerebral I/R injury.

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“…Several studies have shown the important role of small RNA in the molecular mechanisms that control the function of the BBB [182]. For example, the microRNA miR-27a-3p was identified in intracerebral hemorrhage patients to regulate BBB function and edema formation via up-regulation of AQP11 [183]. Therefore, small RNA sequencing is an important tool to better understand the role of small RNAs in the BBB.…”

Section: Design and Preparation Of Sequencing Librariesmentioning

confidence: 99%

Advancing brain barriers RNA sequencing: guidelines from experimental design to publication

Francisco

Marchetti

Rodríguez‐Lorenzo

et al. 2020

Fluids Barriers CNS

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Background: RNA sequencing (RNA-Seq) in its varied forms has become an indispensable tool for analyzing differential gene expression and thus characterization of specific tissues. Aiming to understand the brain barriers genetic signature, RNA seq has also been introduced in brain barriers research. This has led to availability of both, bulk and single-cell RNA-Seq datasets over the last few years. If appropriately performed, the RNA-Seq studies provide powerful datasets that allow for significant deepening of knowledge on the molecular mechanisms that establish the brain barriers. However, RNA-Seq studies comprise complex workflows that require to consider many options and variables before, during and after the proper sequencing process. Main body: In the current manuscript, we build on the interdisciplinary experience of the European PhD Training Network BtRAIN (https ://www.btrai n-2020.eu/) where bioinformaticians and brain barriers researchers collaborated to analyze and establish RNA-Seq datasets on vertebrate brain barriers. The obstacles BtRAIN has identified in this process have been integrated into the present manuscript. It provides guidelines along the entire workflow of brain barriers RNA-Seq studies starting from the overall experimental design to interpretation of results. Focusing on the vertebrate endothelial blood-brain barrier (BBB) and epithelial blood-cerebrospinal-fluid barrier (BCSFB) of the choroid plexus, we provide a step-by-step description of the workflow, highlighting the decisions to be made at each step of the workflow and explaining the strengths and weaknesses of individual choices made. Finally, we propose recommendations for accurate data interpretation and on the information to be included into a publication to ensure appropriate accessibility of the data and reproducibility of the observations by the scientific community. Conclusion: Next generation transcriptomic profiling of the brain barriers provides a novel resource for understanding the development, function and pathology of these barrier cells, which is essential for understanding CNS homeostasis and disease. Continuous advancement and sophistication of RNA-Seq will require interdisciplinary approaches between brain barrier researchers and bioinformaticians as successfully performed in BtRAIN. The present guidelines are built on the BtRAIN interdisciplinary experience and aim to facilitate collaboration of brain barriers researchers with bioinformaticians to advance RNA-Seq study design in the brain barriers community.

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

Cited by 95 publications

References 40 publications

AQP1 and AQP4 Contribution to Cerebrospinal Fluid Homeostasis

AQP1 and AQP4 Contribution to Cerebrospinal Fluid Homeostasis

Circ-camk4 involved in cerebral ischemia/reperfusion induced neuronal injury

Advancing brain barriers RNA sequencing: guidelines from experimental design to publication

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