miR-7 通过 HoxB3 和 PI3K/AKT/mTOR 信号通路减少视网膜色素上皮细胞中高糖诱导的损伤。
miR-7 Reduces High Glucose Induced-damage Via HoxB3 and PI3K/AKT/mTOR Signaling Pathways in Retinal Pigment Epithelial Cells.
机构信息
Department of Ophthalmology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
出版信息
Curr Mol Med. 2020;20(5):372-378. doi: 10.2174/1566524019666191023151137.
BACKGROUND
Diabetic retinopathy (DR) is a common complication of diabetes. This study investigated the effect of miR-7 in the regulation of cell proliferation via the HoxB3 gene and PI3K/AKT/mTOR signaling pathways in DR.
METHODS
Human retinal pigment epithelial cell line (ARPE-19) cultured in normal medium (Control) and high glucose medium (25mM glucose, HG) was transfected with mimics NC (HG+ mimics NC), miR-7 mimics (HG+miR-7 mimics), inhibitor NC (HG+ inhibitor NC), and miR-inhibitor (HG+miR-7 inhibitor). The cells were assayed for viability, apoptosis, and expression of genes.
RESULTS
HG reduced cell viability and increased apoptosis. However, miR-7 mimics reduced the apoptosis. PCR results showed that miR-7 was significantly upregulated after transfection with miR-7 mimics. The expression of Hoxb3, mTOR, p-PI3K, and p- AKT was significantly downregulated at mRNA and protein levels after miR-7 mimics transfection, while no difference was observed for PI3K and AKT expression.
CONCLUSION
Our findings demonstrate that miR-7 regulates the growth of retinal epithelial cells through various pathways and is a potential therapeutic target for the prevention and treatment of diabetic retinopathy.
背景
糖尿病视网膜病变（DR）是糖尿病的常见并发症。本研究探讨了 miR-7 通过 HoxB3 基因和 PI3K/AKT/mTOR 信号通路对 DR 中细胞增殖的调节作用。
方法
在正常培养基（对照）和高葡萄糖培养基（25mM 葡萄糖，HG）中培养人视网膜色素上皮细胞系（ARPE-19），用 mimics NC（HG+ mimics NC）、miR-7 mimics（HG+miR-7 mimics）、inhibitor NC（HG+inhibitor NC）和 miR-inhibitor（HG+miR-7 inhibitor）转染。检测细胞活力、凋亡和基因表达。
结果
HG 降低细胞活力并增加细胞凋亡，而 miR-7 mimics 则减少细胞凋亡。PCR 结果显示，转染 miR-7 mimics 后 miR-7 表达显著上调。miR-7 mimics 转染后，mRNA 和蛋白水平上 Hoxb3、mTOR、p-PI3K 和 p-AKT 的表达显著下调，而 PI3K 和 AKT 的表达无差异。
结论
我们的研究结果表明，miR-7 通过多种途径调节视网膜上皮细胞的生长，是预防和治疗糖尿病视网膜病变的潜在治疗靶点。
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