长链非编码 RNA H19 可防止糖尿病视网膜病变中的内皮-间充质转化。
lncRNA H19 prevents endothelial-mesenchymal transition in diabetic retinopathy.
机构信息
Department of Pathology and Laboratory Medicine, Western University, Dental Science Building 4033, 1151 Richmond Street, London, ON, N6A 5C1, Canada.
Department of Ophthalmology, Western University, London, ON, Canada.
出版信息
Diabetologia. 2019 Mar;62(3):517-530. doi: 10.1007/s00125-018-4797-6. Epub 2019 Jan 5.
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.
目的/假设：糖尿病视网膜病变的病理生理学与高血糖及其对视网膜微血管组织的影响有关。由此产生的内皮损伤将内皮细胞表型改变为获得间充质特性（即内皮-间充质转化[EndMT]）。这种变化可以通过表观遗传机制来调节，包括长非编码 RNA（lncRNA）。lncRNA H19 可能通过 TGF-β 影响 EndMT。我们研究了 H19 在糖尿病视网膜病变中调节 EndMT 的作用。
方法
在暴露于不同葡萄糖水平的人视网膜内皮细胞中过表达或沉默 H19。检查细胞中 H19、内皮和间充质标志物的表达情况。然后，我们将研究扩展到糖尿病视网膜病变小鼠模型的视网膜组织，并检查增殖性糖尿病视网膜病变患者的玻璃体样本。
结果
高葡萄糖条件（25mmol/l）下 H19 的表达下调。H19 的过表达可阻止葡萄糖诱导的 EndMT。这种变化似乎通过一种 Smad 非依赖性机制涉及 TGF-β。糖尿病导致视网膜 H19 的下调。使用 H19 敲除小鼠，我们在视网膜中观察到类似的 EndMT。对增殖性糖尿病视网膜病变患者玻璃体样本的检查也证实了糖尿病中 H19 的下调。
结论/解释：因此，我们得出结论，H19 通过特定机制调节糖尿病视网膜病变中的 EndMT。
数据可用性
我们之前的微阵列结果可以通过 GEO 注册号 GSE122189 在网上找到。
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