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Diabetologia

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01-03-2019 | Diabetic Retinopathy | Article

lncRNA H19 prevents endothelial–mesenchymal transition in diabetic retinopathy

Authors: Anu A. Thomas, Saumik Biswas, Biao Feng, Shali Chen, John Gonder, Subrata Chakrabarti

Published in: Diabetologia | Issue 3/2019

Abstract

Aims/hypothesis

The pathophysiology of diabetic retinopathy is linked to hyperglycaemia and its effect on retinal microvascular tissues. The resulting endothelial injury changes the endothelial cell phenotype to acquire mesenchymal properties (i.e. endothelial–mesenchymal transition [EndMT]). Such changes can be regulated by epigenetic mechanisms, including long non-coding RNAs (lncRNAs). lncRNA H19 may influence EndMT through TGF-β. We investigated the role of H19 in regulating EndMT during diabetic retinopathy.

Methods

H19 was overexpressed or silenced in human retinal endothelial cells exposed to various glucose levels. The cells were examined for H19, endothelial and mesenchymal markers. We then expanded the study to retinal tissues in a mouse model of diabetic retinopathy and also examined vitreous humour samples from individuals with proliferative diabetic retinopathy.

Results

Expression of H19 was downregulated in high glucose conditions (25 mmol/l). H19 overexpression prevented glucose-induced EndMT. Such changes appear to involve TGF-β through a Smad-independent mechanism. Diabetes caused downregulation of retinal H19. Using H19 knockout mice, we demonstrated similar EndMT in the retina. Examination of vitreous humour from individuals with proliferative diabetic retinopathy also reinforced the downregulation of H19 in diabetes.

Conclusions/interpretation

We therefore concluded that H19 regulates EndMT in diabetic retinopathy through specific mechanisms.

Data availability

The results from our previous microarray can be found online using the GEO accession number GSE122189.

Available only for authorised users

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Title: lncRNA H19 prevents endothelial–mesenchymal transition in diabetic retinopathy
Authors: Anu A. Thomas
Saumik Biswas
Biao Feng
Shali Chen
John Gonder
Subrata Chakrabarti
Publication date: 01-03-2019
Publisher: Springer Berlin Heidelberg
Keywords: Diabetic Retinopathy
Diabetic Retinopathy
Published in: Diabetologia / Issue 3/2019
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-018-4797-6

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lncRNA H19 prevents endothelial–mesenchymal transition in diabetic retinopathy

Abstract

Aims/hypothesis

Methods

Results

Conclusions/interpretation

Data availability

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Abstract

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