lncRNA H19 prevents endothelial–mesenchymal transition in diabetic retinopathy

Thomas, Anoop; Biswas, Saumik; Feng, Biao; Chen, Shali; Gonder, John R.; Chakrabarti, Subrata

doi:10.1007/s00125-018-4797-6

Cited by 162 publications

(165 citation statements)

References 59 publications

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“…lncRNAs of RNCR2, NEAT2, CDKN2B-AS1, and PVT1 have shown significant diagnostic performance in DR progression [27], and lncRNA-MALAT1 promotes neovascularization in DR through regulating the miR-125b/VE-cadherin axis [28]. lncRNA H19 prevents endothelial-mesenchymal transition in DR [29].The long non-coding RNA of maternally expressed gene 3 (lncRNA-MEG3)/miR223/NLRP3 inflammasome gene axis is thought to play a significant role in pyroptosis of endothelial cells [30]. The decrease in lncRNA-MEG3 could enhance retinal vessel dysfunction through the PI3k/Akt signaling pathway [31].…”

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confidence: 99%

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Transthyretin Upregulates Long Non-Coding RNA MEG3 by Affecting PABPC1 in Diabetic Retinopathy

Fan

Zhang

et al. 2019

IJMS

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The aim of the study was to demonstrate how transthyretin (TTR) could affect long non-coding RNA (lncRNA) of maternally expressed gene 3 (MEG3) and play important roles in diabetic retinopathy (DR). A DR model in C57BL/6 mice was established after intraperitoneal injection of streptozotocin (STZ). After intravitreal injection with TTR pAAV vector, MEG3 short hairpin RNA (shRNA), scrambled shRNA, or MEG3, retinal imaging, retinal trypsin digestion, and fundus vascular permeability tests were performed. Cell counting kit-8 (CCK8), transwell, and Matrigel assays were employed to detect the proliferation and migration of human retinal microvascular endothelial cells (hRECs). The binding between long non-coding RNA of maternally expressed gene 3 (lncRNA-MEG3) and microRNA-223-3p (miR-223-3p) was observed by using luciferase reporter assays, while co-immunoprecipitation (co-IP) was employed to confirm the interaction between TTR and the target. In the DR mice model, retinal vascular leakage and angiogenesis were repressed by overexpressing TTR. In vitro, the added TTR promoted the level of lncRNA-MEG3 by interacting with poly (A) binding protein cytoplasmic 1 (PABPC1), and then repressed proliferation and angiogenesis of hRECs. In vivo, silencing or overexpressing lncRNA-MEG3 significantly affected retinal vascular phenotypes. Additionally, the interaction between lncRNA-MEG3 and miR-223-3p was confirmed, and silencing of miR-223-3p revealed similar effects on hRECs as overexpression of lncRNA-MEG3. In summary, in the DR environment, TTR might affect the lncRNA MEG3/miR-223-3p axis by the direct binding with PABPC1, and finally repress retinal vessel proliferation.Keywords: diabetic retinopathy (DR); transthyretin (TTR); long non-coding RNA (lncRNA); maternally expressed gene 3 (MEG3); polyadenylate-binding protein cytoplasmic 1 (PABPC1) Int.In the eyes, transthyretin (TTR) is mainly expressed in human retinal pigment epithelial cells (hRPECs) and the choroid [7], and it usually works as the carrier of thyroxine (T4) and retinol [8,9]. As previously reported, TTR should be correlated with diabetes-associated diseases, e.g., type I diabetes patients showed lower serum TTR levels [10]. In clinical investigations, myopia was revealed to protect diabetic patients from suffering DR [11,12]. Our previous work has demonstrated that higher vitreous TTR content of high myopia patient [13] might help to prevent the progression of DR [14]. The serum and vitreous TTR levels in DR patients were associated with DR progression [15]; TTR suppressed angiogenesis by affecting the angiopoietin-Tie signaling pathway in hyperglycemia [16], and enhanced the apoptosis of hRECs through a hypoxia-associated 78-kDa glucose-regulated protein (GRP78)-dependent pathway [17]. Still, the regulatory mechanisms involving TTR in DR are not entirely clear.Long non-coding RNAs (lncRNAs) regulate targeted mRNA expression via the microRNA (miRNA) response element known as competing endogenous RNA (ceRNA) [18,19]. LncRNAs are known to play vital roles in oc...

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confidence: 99%

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confidence: 99%

Transthyretin Upregulates Long Non-Coding RNA MEG3 by Affecting PABPC1 in Diabetic Retinopathy

Fan

Zhang

et al. 2019

IJMS

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“…In a recent study involving retinal endothelial cells exposed to glucose and a mouse model of DR, Thomas et al showed that H19 is involved in EMT in the retina. They also demonstrated hyperglycemia-induced downregulation of H19 in the vitreous humor from individuals with PDR compared to non-diabetic controls [12]. Nevertheless, it is important to note that lncRNAs have cell and tissue-specific expression [32], where they regulate homeostasis and the expression of protein-coding or other noncoding RNA genes [33].…”

Section: Discussionmentioning

confidence: 99%

“…In the current study, we explored the potential role of H19 and GAS5 lncRNAs in T2DM and DR considering the following: 1) their implication in DM-and DR-related cellular pathways; 2) to the best of our knowledge, the circulating levels of H19 and GAS5 have not been evaluated in DM/DR in our population before; 3) although the levels of circulating lncRNAs have been associated with the development of DR [18,19], most of the previous studies focused on diabetic rat models or endothelial cells cultured in high-glucose conditions [12,20,21]. Here, we compared the plasma levels of circulating H19 and GAS5 lncRNAs of T2DM patients (with/ without DR) and healthy controls.…”

Section: Introductionmentioning

confidence: 99%

Circulating long noncoding RNAs H19 and GAS5 are associated with type 2 diabetes but not with diabetic retinopathy: A preliminary study

Fawzy

Abdelghany

Toraih

et al. 2020

Bosn J of Basic Med Sci

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Recently, a wide range of biological and pathological roles of long noncoding RNAs (lncRNAs) have been discovered. However, the potential role of circulating lncRNAs H19 and GAS5 in type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR) is not clear. Here, we assessed the plasma levels of H19 and GAS5 lncRNAs in T2DM patients with/without DR and evaluated if H19 and GAS5 pre-treatment plasma levels are a predictor of early response to a single aflibercept dose in DR subgroup. Plasma lncRNA expression profiles of 119 T2DM patients (66 with DR and 53 without DR) and 110 healthy controls were determined by quantitative reverse transcription PCR. The association of lncRNA expression profiles with clinical features and aflibercept early response in DR patients was investigated. Relative H19 expression levels were significantly increased in T2DM group (including DR and non-DR subgroups) vs. controls, while GAS5 levels were decreased in T2DM group (p < 0.001).

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“…However, its pathogenesis is complicated and not fully understood. Previous studies suggested that a series of pathophysiological changes happened on the retina under the stimulation of persistent hyperglycemia, resulting in retinopathy [4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

miR-874 ameliorates retinopathy in diabetic rats by NF-κB signaling pathway

Yuan

Zhao

et al. 2020

Preprint

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Background: miRNAs participate in the development and progression of diabetic retinopathy (DR) and are involved in multiple pathogenesis of DR. High expression of NF-κB signaling pathway boosts the progression of retinopathy in diabetes rats. We found a site where miR-874 bound to the NF-κB p65 by the prediction on a bioinformatics website. Therefore, it was speculated that miR-874 might improve retinopathy in diabetic rats by inhibiting the NF-κB signaling pathway.Methods: Ten healthy Sprague-Dawley rats were taken as the control group. Sixty streptozotocin (60 mg/kg)-induced diabetes model rats were randomly divided into the model group (injection of normal saline), negative control (NC) agomir group (injection of overexpressed NC vector), miR-874 agomir group (injection of miR-874 mimic), miR-874 anti-agomir group (injection of miR-874 inhibitor), EVP4593 group (injection of NF-κB signaling pathway antagonist EVP4593), and miR-874 anti-agomir + EVP4593 group (injection of miR-874 inhibitor and EVP4593). All injection was via caudal vein.Results: miR-874 could target the degradation of p65. Compared with the control group, there were significantly reduced miR-874 expression, increased VEGF and Ang2 protein expressions, lowered end-diastolic velocity and peak systolic velocity of central retinal artery (CRA) and blood velocity of central retinal vein and CRA, heightened plasma viscosity, blood viscosity and erythrocyte sedimentation rate at all shear rates, decreased capillary pericytes, increased vascular endothelial cells, and ascended p65 expression in the retina of rats in the model group (all P < 0.05). It showed that pathological changes appeared in the retina of diabetes rats. These indexes showed the same results after miR-874 was inhibited (all P < 0.05). However, these indexes showed the opposite results in the miR-874 agomir group and EVP4593 group compared with the model group (all P < 0.05). EVP4593 could alleviate the aggravation of retinopathy that was caused by the inhibition of miR-874 in diabetes rats.Conclusions: miR-874 mediates the NF-κB signaling pathway by targeting the degradation of p65 to further improve the retina of diabetes rats, showing the improvement effect of miR-874 on diabetic retinopathy in rats.

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lncRNA H19 prevents endothelial–mesenchymal transition in diabetic retinopathy

Cited by 162 publications

References 59 publications

Transthyretin Upregulates Long Non-Coding RNA MEG3 by Affecting PABPC1 in Diabetic Retinopathy

Transthyretin Upregulates Long Non-Coding RNA MEG3 by Affecting PABPC1 in Diabetic Retinopathy

Circulating long noncoding RNAs H19 and GAS5 are associated with type 2 diabetes but not with diabetic retinopathy: A preliminary study

miR-874 ameliorates retinopathy in diabetic rats by NF-κB signaling pathway

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