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

Rom, Slava; Dykstra, Holly; Zuluaga-Ramirez, Viviana; Reichenbach, Nancy L.; Persidsky, Yuri

doi:10.1038/jcbfm.2015.154

Cited by 104 publications

(116 citation statements)

References 39 publications

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“…Another study has analyzed the therapeutic manipulation of brain endothelial microRNA‐98 and Let‐7g‐3p to prevent BBB dysfunction in neuroinflammation. In this study, the authors identified 2 potential targets, CCL2 and CCL5, by which microRNA‐98 and Let‐7g‐3p may regulate leukocyte adhesion (34). These studies suggest that a brain endothelial microRNA therapeutic strategy aimed at ameliorating BBB dysfunction during neuroinflammation may be beneficiated as a result of microRNAs concomitantly modulating several molecular and cellular processes implicated in neuroinflammation.…”

Section: Therapeutic Potential Of Brain Endothelial Micrornas For Cnsmentioning

confidence: 99%

Regulation of brain endothelial barrier function by microRNAs in health and neuroinflammation

Lopez-Ramirez

Reijerkerk²,

Vries

et al. 2016

FASEB j.

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Brain endothelial cells constitute the major cellular element of the highly specialized blood-brain barrier (BBB) and thereby contribute to CNS homeostasis by restricting entry of circulating leukocytes and blood-borne molecules into the CNS. Therefore, compromised function of brain endothelial cells has serious consequences for BBB integrity. This has been associated with early events in the pathogenesis of several disorders that affect the CNS, such as multiple sclerosis, HIV-associated neurologic disorder, and stroke. Recent studies demonstrate that brain endothelial microRNAs play critical roles in the regulation of BBB function under normal and neuroinflammatory conditions. This review will focus on emerging evidence that indicates that brain endothelial microRNAs regulate barrier function and orchestrate various phases of the neuroinflammatory response, including endothelial activation in response to cytokines as well as restoration of inflamed endothelium into a quiescent state. In particular, we discuss novel microRNA regulatory mechanisms and their contribution to cellular interactions at the neurovascular unit that influence the overall function of the BBB in health and during neuroinflammation.

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Section: Therapeutic Potential Of Brain Endothelial Micrornas For Cnsmentioning

confidence: 99%

Regulation of brain endothelial barrier function by microRNAs in health and neuroinflammation

Lopez-Ramirez

Reijerkerk²,

Vries

et al. 2016

FASEB j.

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“…Let-7g leads to beneficial effects on EC through modulating TGF-β signaling and SIRT-1 signaling (Figure 2) [24], which might contribute to the limitation of local inflammation of plaque and improve vascular thrombosis. In addition, overexpression of let-7g has resulted in the reduction of adhesion and migration of monocytes across endothelium [25].…”

Section: Let-7g and Inflammationmentioning

confidence: 99%

MicroRNA Let-7g and Atherosclerosis Plaque Stabilization

Yin¹,

Zhang²,

Hou³

et al. 2017

WJCD

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Vascular atherosclerotic vulnerable plaque rupture is the primary cause of acute myocardial infarctions and strokes. Thus, stabilization of vulnerable plaques is of important clinical endeavor to decrease the fatal risk of atherosclerosis. Inflammatory infiltration, apoptosis of endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), destruction of extracellular matrix (ECM) or collagen, and neovascularization all contribute to the formation and stability of plaque. Let-7g, one miRNA of let-7 family, is related to retardation of the progress of vulnerable atherosclerosis plaque. First of all, let-7g induced preservation on vascular diseases through regulating on the intracellular Ca 2+ -activated protein kinase C-oxLDL-LOX-1 pathway, which resulted in reduced leukocyte adhesion to and migration across endothelium. Over expression of let-7g negatively regulated apoptosis in the ECs by targeting lectin-like oxidized LDL receptor-1(LOX-1)/CASP3 expression, therefore made the fibrous cap of plaque integrated and thick, increased the density of vascular atherosclerotic plaque. In addition, let-7g might stabilize the atherosclerotic plaque through other aspects. In this review, we focus on current and potential importance of let-7g on the stabilization of atherosclerosis plaque which might lead to the future development of an alternative strategy of CAD.

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“…MiRs are key regulators of a vast number of biological processes and disorders, including MS14 and those regulating neurovascular function in inflammation15, such as regulation of cell adhesion molecules and leukocyte adhesion to human brain endothelium1216.…”

mentioning

confidence: 99%

MiR-126 and miR-126* regulate shear-resistant firm leukocyte adhesion to human brain endothelium

Cerutti

Edwards

Vries

et al. 2017

Sci Rep

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Leukocyte adhesion to brain endothelial cells, the blood-brain barrier main component, is a critical step in the pathogenesis of neuroinflammatory diseases such as multiple sclerosis (MS). Leukocyte adhesion is mediated mainly by selectins, cell adhesion molecules and chemokines induced by pro-inflammatory cytokines such as TNFα and IFNγ, but the regulation of this process is not fully clear. This study investigated the regulation of firm leukocyte adhesion to human brain endothelium by two different brain endothelial microRNAs (miRs), miR-126 and miR-126*, that are downregulated by TNFα and IFNγ in a human brain endothelial cell line, hCMEC/D3. Using a leukocyte adhesion in vitro assay under shear forces mimicking blood flow, we observed that reduction of endothelial miR-126 and miR-126* enhanced firm monocyte and T cell adhesion to hCMEC/D3 cells, whereas their increased expression partially prevented THP1, Jurkat and primary MS patient-derived PBMC firm adhesion. Furthermore, we observed that miR-126* and miR-126 downregulation increased E-selectin and VCAM1, respectively, while miR-126 overexpression reduced VCAM1 and CCL2 expression by hCMEC/D3 cells, suggesting that these miRs regulate leukocyte adhesion by modulating the expression of adhesion-associated endothelial mRNA targets. Hence, human brain endothelial miR-126 and miR-126* could be used as a therapeutic tool to reduce leukocyte adhesion and thus reduce neuroinflammation.

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

Cited by 104 publications

References 39 publications

Regulation of brain endothelial barrier function by microRNAs in health and neuroinflammation

Regulation of brain endothelial barrier function by microRNAs in health and neuroinflammation

MicroRNA Let-7g and Atherosclerosis Plaque Stabilization

MiR-126 and miR-126* regulate shear-resistant firm leukocyte adhesion to human brain endothelium

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