MiR-20b targets AKT3 and modulates vascular endothelial growth factor-mediated changes in diabetic retinopathy

Qin, Bo; Liu, Jinwen; Liu, Shenwen; Li, Baijun; Ren, Jing

doi:10.1093/abbs/gmw065

Cited by 30 publications

(30 citation statements)

References 35 publications

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“…Our findings are similar to those of the study by Zampetaki et al, who speculated that miR‐20b was downregulated in plasma of diabetic patients . Also, Qin et al revealed that miR‐20b can directly modulate VEGF‐mediated changes in DR .…”

Section: Discussionsupporting

confidence: 92%

Diagnostic and prognostic role of serum miR‐20b, miR‐17‐3p, HOTAIR, and MALAT1 in diabetic retinopathy

et al. 2018

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Noncoding RNAs are emerging biomarkers for many diseases including diabetic retinopathy (DR). This study aimed to measure the expression levels of serum miR‐20b, miR‐17‐3p, HOTAIR, and MALAT1 in DR patients. A total of 80 patients diagnosed as type 2 diabetes (T2D) and 81 healthy subjects were recruited in this study. T2D patients were divided into three groups: nondiabetic retinopathy (NDR) group (30 patients), nonproliferative diabetic retinopathy (NPDR) group (30 patients), and proliferative diabetic retinopathy (PDR) group (20 patients). Quantitative real‐time polymerase chain reaction (PCR) was used to assess the expression of serum miR‐20b, miR‐17‐3p, HOTAIR, and MALAT1. We found a significant decrease in serum miR‐20b and a significant increase in serum HOTAIR and MALAT1 in NDR patients compared to healthy subjects. Also, we revealed a significant decrease in serum miR‐20b and miR‐17‐3p and a significant increase in serum HOTAIR and MALAT1 in each of NPDR and PDR groups when compared with healthy subjects. Furthermore, we reported a significant decrease in miR‐20b and miR‐17‐3p and a significant increase in HOTAIR and MALAT1in DR as well as in PDR patients when compared with NDR patients. However, on comparing NPDR with NDR patients, no significant difference was observed regarding the expression levels of miR‐20b and miR‐17‐3p, in contrast, significant elevation of serum HOTAIR and MALAT1 was found in NPDR. Moreover, we observed a significant decrease in serum miR‐20b and miR‐17‐3p and a significant increase in serum HOTAIR and MALAT1 in PDR group relative to NPDR group. Receiver operating characteristic (ROC) curve was used for evaluating the diagnostic value of the examined serum noncoding RNAs as novel biochemical indicators detecting severity of DR. Our analyses suggested that the examined serum noncoding RNAs may discriminate DR (PDR and NPDR) from NDR. Furthermore, these noncoding RNAs (less importantly miR‐17) can be used as promising novel biomarkers for prediction DR severity, distinguishing PDR from NPDR patients. We can conclude that serum miR‐20b, miR‐17‐3p, HOTAIR, and MALAT1 may be used as noninvasive biomarkers for screening of DR and early diagnosis of PDR. © 2018 IUBMB Life, 71(3):310–320, 2019

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Section: Discussionsupporting

confidence: 92%

Diagnostic and prognostic role of serum miR‐20b, miR‐17‐3p, HOTAIR, and MALAT1 in diabetic retinopathy

et al. 2018

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“…Our results also showed that miR-15a/16 reduced endothelial cell permeability through downregulation of VEGF in REC under high glucose conditions. Inductive roles of VEGF on endothelial permeability have been reported in previous studies (Fischer et al, 1999; Qin et al, 2016; Yun et al, 2016). …”

Section: Discussionsupporting

confidence: 74%

“…Previous studies have shown a regulatory role for VEGF on endothelial barrier functions in vitro (Fischer et al, 1999; Qin, Liu, Liu, Li, & Ren, 2016). Additionally, the blockade of VEGFR1 suppressed vascular leakage and disorganization of ZO-1 (He et al, 2015).…”

Section: Resultsmentioning

confidence: 97%

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miR-15a/16 inhibits TGF-beta3/VEGF signaling and increases retinal endothelial cell barrier proteins

Liu

Steinle

2017

Vision Research

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Hyperglycemia is a significant risk factor for diabetic retinopathy and induces multiple biochemical changes, including inflammation and endothelial dysfunction in the retina. Alterations in microRNA expression have been implicated in the pathological responses of diabetic retinopathy and the manipulation of microRNA may provide powerful strategy for therapeutics. Among the predicted targets of miR-15a and -16 are TGF-beta3, SMAD2/3, and VEGF, all of which are known to play a role in vascular endothelial functions. The purpose of this study was to investigate the hypothesis that miR-15a/16 inhibits TGF-beta3/VEGF signaling to maintain retinal endothelial cell barrier protein levels. Human primary retinal endothelial cells (REC) were maintained in normal (5 mM) glucose or transferred to high glucose medium (25 mM) for 3 days. REC were transfected with miRNA mimics (hsa-miR-15a-5p and -16-5p). Retinal lysates from miR-15a-transgenic mice were also analyzed. We demonstrated that overexpression of miR-15a/16 resulted in decreased TGF-beta3 signaling and VEGF levels in cultured REC grown in high glucose conditions. In addition, the levels of tight junction proteins, zonula occludens-1 (ZO-1) and occludin, were elevated in REC following overexpression of miR-15a and -16. Overexpression of miR-15a and - 16 played a role in reducing cellular permeability through inhibition of VEGF signaling in REC cultured under high glucose conditions. Using miR-15a-transgenic mice, we demonstrated the regulatory role of miR-15a on TGF-beta3 signaling and tight junction proteins in vivo. Our outcomes suggest that miR-15a/16 maintain the retinal endothelial cell barrier by reducing TGFbeta3/VEGF signaling and increasing levels of key tight junction proteins.

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“…SIRT4 is also associated with photoaged skin and stress‐induced cellular senescence, which linked senescence‐associated mitochondrial dysfunction to both miR‐15b and SIRT4 . Moreover, miR‐20b upregulated by PUFAs directly targets AKT3, and AKT3 silencing decreases the levels of VEGF . Specifically, in primary ECs, VEGF stimulation and the downstream mitochondrial biogenesis process required AKT3, and the blockade of AKT3 also reduces PGC‐1α‐dependent gene expression .…”

Section: Developing Leads To Extend Our Understanding Of Redox Contromentioning

confidence: 99%

Redox control of vascular biology

et al. 2019

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Redox control is lost when the antioxidant defense system cannot remove abnormally high concentrations of signaling molecules, such as reactive oxygen species (ROS). Chronically elevated levels of ROS cause oxidative stress that may eventually lead to cancer and cardiovascular and neurodegenerative diseases. In this review, we focus on redox effects in the vascular system. We pay close attention to the subcompartments of the vascular system (endothelium, smooth muscle cell layer) and give an overview of how redox changes influence those different compartments. We also review the core aspects of redox biology, cardiovascular physiology, and pathophysiology. Moreover, the topic‐specific knowledgebase DES‐RedoxVasc was used to develop two case studies, one focused on endothelial cells and the other on the vascular smooth muscle cells, as a starting point to possibly extend our knowledge of redox control in vascular biology.

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MiR-20b targets AKT3 and modulates vascular endothelial growth factor-mediated changes in diabetic retinopathy

Cited by 30 publications

References 35 publications

Diagnostic and prognostic role of serum miR‐20b, miR‐17‐3p, HOTAIR, and MALAT1 in diabetic retinopathy

Diagnostic and prognostic role of serum miR‐20b, miR‐17‐3p, HOTAIR, and MALAT1 in diabetic retinopathy

miR-15a/16 inhibits TGF-beta3/VEGF signaling and increases retinal endothelial cell barrier proteins

Redox control of vascular biology

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