Hypoxia-Induced Deregulation of miR-126 and Its Regulative Effect on VEGF and MMP-9 Expression

Ye, Panpan; Liu, Jian; He, Fei; Xu, Wen; Yao, Ke

doi:10.7150/ijms.7329

Cited by 98 publications

(82 citation statements)

References 22 publications

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“…In addition, a decrease in VEGF in the miR-126 inhibitor group and an increase in VEGF in the miR-216 mimic group were found in their study, suggesting the miR-126 expression might be negatively correlated with the VEGF level in HCMECs [39]. However, a previous study revealed that the level of miR-126 is decreased under hypoxic conditions and subsequently reduces the expression of VEGF both in vitro and in vivo [40]. Those results indicate that miR-126 might play a dual role in the regulation of the VEGF level, which might explain the insignificant correlation of miR-126 with the VEGF level in our study.…”

Section: Discussionmentioning

confidence: 85%

miR-126 in Peripheral Blood Mononuclear Cells Negatively Correlates with Risk and Severity and is Associated with Inflammatory Cytokines as well as Intercellular Adhesion Molecule-1 in Patients with Coronary Artery Disease

Zhang²

2018

Cardiology

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Objectives: The aim of this study was to evaluate the association of miR-126 with risk and severity of coronary artery disease (CAD) as well as its correlation with inflammatory cytokines and endothelial related proteins. Methods: In total, 215 patients suspected of CAD who underwent coronary angiography were enrolled in this case control study and were divided into a CAD group (n = 119) and control group (n = 96). miR-126 relative expression was assessed by real-time polymerase chain reaction. Results: The relative expression of miR-126 decreased in CAD patients compared to controls (p < 0.001), and the receiver operating characteristic curve showed a good diagnostic value of miR-126 for CAD risk with an area under the curve of 0.801 (95% CI 0.740-0.861). Additionally, miR-126 was negatively correlated with high-sensitivity C-reactive protein levels (p < 0.001) and reversely associated with TNF-α (p = 0.008) and IL-6 (p < 0.001) levels, while it was positively correlated with the IL-10 level (p < 0.001). In addition, miR-126 was negatively associated with intercellular adhesion molecule-1 (ICAM-1) levels (p = 0.001), and no association of miR-126 with vascular endothelial growth factor was detected (p = 0.142). Meanwhile, the miR-126 relative level was negatively associated with the Gensini score (p < 0.001). Conclusions: Peripheral blood mononuclear cell miR-126 predicts risk and severity and correlates with inflammatory cytokines as well as ICAM-1 in patients with CAD.

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Section: Discussionmentioning

confidence: 85%

miR-126 in Peripheral Blood Mononuclear Cells Negatively Correlates with Risk and Severity and is Associated with Inflammatory Cytokines as well as Intercellular Adhesion Molecule-1 in Patients with Coronary Artery Disease

Zhang²

2018

Cardiology

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“…These are consistent with previous publications. 23,26,36 The other mechanism relevant to AMD is miR-126-3p regulation of VEGF-A in RPE cells through a novel mechanism of repressing CryaB promoter activity. CryaB is a chaperone protein that can protect VEGF and other factors from denaturation and destabilization.…”

Section: Cell Type-specific Function Of Mir-126 In Angiogenesis and Cnvmentioning

confidence: 99%

Strand and Cell Type-specific Function of microRNA-126 in Angiogenesis

et al. 2016

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microRNAs or miRs have been shown to be pivotal modulators of vascular development. The strand and cell typespecific function of miR-126 in angiogenesis, especially pathological angiogenesis, remains poorly defined. We characterized the retinal vascular phenotype of miR-126 −/− mice, and tested the function of miR-126 strands (miR-126-3p and -5p) using in vitro angiogenesis models and a mouse model of neovascular age-related macular degeneration. We found that miR-126 is critical for retinal vascular development but has dual function in pathological angiogenesis. miR-126 −/− mice showed defective postnatal retinal vascular development and remodeling, which is partially rescued by genetic knockout of its target gene Spred-1. Surprisingly, either silencing miR-126-3p by LNA-antimiR or overexpressing miR-126-3p by miRNA mimic repressed laser-induced choroidal neovascularization. To dissect the underlying mechanism, we found in endothelial cells, silencing of miR-126-3p repressed angiogenesis, while overexpression of miR-126-5p enhanced angiogenesis. However, in retinal pigment epithelial cells, miR-126-3p repressed vascular endothelial growth factor (VEGF-A) expression via a novel mechanism of regulating αB-Crystallin promoter activity and by directly targeting VEGF-A 3′-untranslated region. These findings provide first genetic evidence that miR-126 is required for the development of different retinal vascular layers, and also uncover a strand and cell type-specific function of miR-126 in ocular pathological angiogenesis. Received 17 March 2016; accepted 11 May 2016; advance online publication 21 June 2016 advance online publication 21 June . doi:10.1038 advance online publication 21 June /mt.2016 INTRODUCTIONThe retina has been an excellent model to study developmental and pathological angiogenesis. Vascularization of the mouse outer retina occurs through two waves of angiogenesis after birth, when endothelial cells (ECs) sprout from the central retinal artery to the peripheral region and then to the intermediate and deep layers of the retinal vascular plexus.1,2 Pathological angiogenesis in the eye is the most common cause of blindness at all ages and underlies conditions such as retinopathy of prematurity in children, diabetic retinopathy in young adults and age-related macular degeneration (AMD) in the elderly. AMD is a degenerative disease of the retina and the leading cause of blindness among the elderly.3 Neovascular (or wet) AMD, which accounts for the majority of acute vision loss in AMD, is characterized by choroidal neovascularization (CNV), a process involving abnormal growth of blood vessels from the choroid into the retina. Vascular endothelial growth factor (VEGF), which is highly expressed in the retinal pigment epithelial (RPE) cells in the eye, is a major cytokine driving neovascularization and vascular permeability during CNV. Several FDA-approved anti-VEGF agents, including Macugen, Lucentis and Eylea, are the current mainstay for wet AMD treatment. 4-6Although anti-VEGF agents have marked...

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“…In the retina, miRNA levels in eye diseases may be different from those levels under normal conditions [1][2][3][4][5] ; this can influence the over-or underexpression of their target genes. This may result in pathological changes, such as the formation of abnormal vessels, inflammation, or angiogenesis [6][7][8] .…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-126 Reduces Blood-Retina Barrier Breakdown via the Regulation of VCAM-1 and BCL2L11 in Ischemic Retinopathy

Bai¹,

Luo²,

Zhang

et al. 2017

Ophthalmic Res

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To evaluate the role of microRNA-126 (miR-126) in maintaining the integrity of the blood-retina barrier (BRB), we established a mouse model of oxygen-induced retinopathy (OIR) and measured the retinal levels of miR-126 using recombinant plasmid pCMV-MIR or pCMV-MIR-126 intravitreal injections. We also detected VCAM-1 and BCL2L11 levels. Retinal vaso-obliteration, VCAM-1 localization on retinal endothelial cells, the blood-retina vascular permeability or albumin leakage in retinas, TUNEL histology, Evans blue assays, or Western blotting for detecting albumin or tight junction levels in the retina was performed. We also detected the effect of miR-126 on the survival of Müller cells in a mouse model using vimentin fluorescence staining. Our results suggested that miR-126 may not only regulate the overexpression of VCAM-1 or BCL2L11 and lead to the reduction of retinal endothelial cell apoptosis, retinal vascular leakage, or retinal permeability in the OIR mouse model, but may also protect hypoxic retinal Müller cells via the STAT3 signaling pathway. We believe that miR-126 could also be a potential therapeutic agent to maintain the stability of the BRB in ischemic retinopathy.

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Hypoxia-Induced Deregulation of miR-126 and Its Regulative Effect on VEGF and MMP-9 Expression

Cited by 98 publications

References 22 publications

miR-126 in Peripheral Blood Mononuclear Cells Negatively Correlates with Risk and Severity and is Associated with Inflammatory Cytokines as well as Intercellular Adhesion Molecule-1 in Patients with Coronary Artery Disease

miR-126 in Peripheral Blood Mononuclear Cells Negatively Correlates with Risk and Severity and is Associated with Inflammatory Cytokines as well as Intercellular Adhesion Molecule-1 in Patients with Coronary Artery Disease

Strand and Cell Type-specific Function of microRNA-126 in Angiogenesis

MicroRNA-126 Reduces Blood-Retina Barrier Breakdown via the Regulation of VCAM-1 and BCL2L11 in Ischemic Retinopathy

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