Department of Ophthalmology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, PR China.
Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, PR China.
Exp Eye Res. 2020 Jan;190:107886. doi: 10.1016/j.exer.2019.107886. Epub 2019 Nov 21.
Diabetic retinopathy (DR) is a microvascular complication of diabetes and one of the most common causes of blindness in active stage. This study is performed to explore the effects of microRNA-21 (miR-21) on retinal vascular endothelial cell (RVEC) viability and angiogenesis in rats with DR via the phosphatidylinositiol 3-kinase/protein kinase B (PI3K/Akt)/vascular endothelial growth factor (VEGF) signaling pathway by binding to phosphatase and tensin homolog (PTEN). Sprague Dawley (SD) rats were used for establishment of DR models. Target relationship between miR-21 and PTEN was assessed by bioinformatics prediction in combination with dual-luciferase reporter gene assay. Identification of expression of miR-21, PTEN and PI3K/Akt/VEGF signaling pathway-related genes in the retinal tissues was then conducted. In order to assess the contributory role of miR-21 in DR, the RVECs were transfected with mimic or inhibitor of miR-21, or siRNA-PTEN, followed by the detection of expression of PTEN and PI3K/Akt/VEGF-related genes, as well as the measurement of cell viability, cell cycle and apoptosis. Increased expression of miR-21 and PI3K/Akt/VEGF related genes, along with a reduced expression of PTEN was observed in the retinal tissues of DR rats. PTEN was targeted and negatively regulated by miR-21, while the PI3K/Akt/VEGF signaling pathway was activated by miR-21. RVECs transfected with miR-21 inhibitor exhibited promoted viability and angiogenesis, and inhibited apoptosis. To conclude, our results indicated that miR-21 overexpression could potentially stimulate RVEC viability and angiogenesis in rats with DR through activation of the PI3K/Akt/VEGF signaling pathway via repressing PTEN expression, highlighting the potential of miR-21 as a target for DR treatment.
糖尿病性视网膜病变（DR）是糖尿病的微血管并发症之一，也是活跃期失明的最常见原因之一。本研究旨在通过结合双荧光素酶报告基因检测，探讨 microRNA-21（miR-21）通过与磷酸酶和张力蛋白同系物（PTEN）结合对糖尿病大鼠视网膜血管内皮细胞（RVEC）活力和血管生成的影响，从而影响磷脂酰肌醇 3-激酶/蛋白激酶 B（PI3K/Akt）/血管内皮生长因子（VEGF）信号通路。使用 Sprague Dawley（SD）大鼠建立 DR 模型。通过生物信息学预测结合双荧光素酶报告基因检测评估 miR-21 和 PTEN 之间的靶关系。然后检测视网膜组织中 miR-21、PTEN 和 PI3K/Akt/VEGF 信号通路相关基因的表达。为了评估 miR-21 在 DR 中的作用，用 miR-21 模拟物或抑制剂或 siRNA-PTEN 转染 RVEC，然后检测 PTEN 和 PI3K/Akt/VEGF 相关基因的表达，以及细胞活力、细胞周期和凋亡的测定。DR 大鼠视网膜组织中 miR-21 和 PI3K/Akt/VEGF 相关基因表达增加，PTEN 表达减少。PTEN 是 miR-21 的靶基因并受其负调控，而 miR-21 激活了 PI3K/Akt/VEGF 信号通路。转染 miR-21 抑制剂的 RVEC 表现出促进活力和血管生成，并抑制凋亡。综上所述，我们的结果表明，miR-21 过表达可能通过抑制 PTEN 表达激活 PI3K/Akt/VEGF 信号通路，从而刺激 DR 大鼠 RVEC 的活力和血管生成，提示 miR-21 可能成为 DR 治疗的靶点。
