糖尿病性视网膜病变
血管生成素
下调和上调
视网膜
新生血管
癌症研究
安格普特4
视网膜
细胞生物学
生物
视网膜病变
糖尿病
内分泌学
血管生成
神经科学
血管内皮生长因子
基因
生物化学
血管内皮生长因子受体
作者
Zifan Xu,Jing Yang,Haohan Zheng,Tianhua Xie,Qian Yang,Jiping Cai,Chao Sun,Yu-Juan Cao,Mei‐Li Wu,Yanqiu Li,Yuqing Cui,Yong Yao,Xiaolu Wang
出处
期刊:Diabetes
[American Diabetes Association]
日期:2023-04-21
卷期号:72 (7): 1012-1027
被引量:1
摘要
Diabetic retinopathy (DR) is a common complication in patients with diabetes, and proliferative DR (PDR) has become an important cause of blindness; however, the mechanisms involved have not been fully elucidated. miRNAs and long noncoding RNAs can play an important role in DR, and they can accurately regulate the expression of target genes through a new regulatory model: competing endogenous RNAs. We isolated total RNA of extracellular vesicles (EVs) in the serum of healthy individuals and individuals with diabetes without DR, non-PDR, or PDR, and performed deep sequencing. We found aberrantly low expression of PPT2-EGFL8 and significantly increased level of miR-423-5p. PPT2-EGFL8 adsorbs miR-423-5p as a molecular sponge and inhibits hypoxia-induced human retinal microvascular endothelial cells proliferation. In an oxygen-induced retinopathy (OIR) model and a streptozotocin-induced diabetes model, Egfl8-overexpression treatment reduces diabetes-related reactive gliosis, inflammation, and acellular capillaries and attenuates the development of pathological neovascularization. In addition, PPT2-EGFL8 targeting miR-423-5p plays an important role in hypoxia-induced peroxisome proliferator-activated receptor-β/δ (PPARD)/angiopoietin-like 4 (ANGPTL4) signaling activation, especially the expression of the C-terminal ANGPTL4 fragment. Finally, ANGPTL4 significantly induces retinal vessel breakage in the inner limiting membrane and facilitates retinal vessel sprouting into the vitreous in the OIR mice. Thus, either new biomarkers or new therapeutic targets may be identified with translation of these findings.
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