Repression of microRNA-21 inhibits retinal vascular endothelial cell growth and angiogenesis via PTEN dependent-PI3K/Akt/VEGF signaling pathway in diabetic retinopathy
Repression of microRNA-21 inhibits retinal vascular endothelial cell growth and angiogenesis via PTEN dependent-PI3K/Akt/VEGF signaling pathway in diabetic retinopathy
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DOI：
10.1016/j.exer.2019.107886
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发表时间：
2020-01-01
影响因子：
3.4
通讯作者：
Qin, Xiu-Hong
中科院分区：
文献类型：
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作者：
Lu, Jian-Min;Zhang, Zhen-Zhen;Qin, Xiu-Hong
糖尿病视网膜病变（diabetic retinopathy，DR）是糖尿病的一种微血管并发症，是活动期最常见的致盲原因之一。本研究旨在探讨microRNA-21（miR-21）通过与磷酸酶和张力蛋白同源物（PTEN）结合，通过磷脂酰肌醇3-激酶/蛋白激酶B（PI 3 K/Akt）/血管内皮生长因子（VEGF）信号通路对DR大鼠视网膜血管内皮细胞（RVEC）活力和血管生成的影响。采用SD（Sprague道利）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分析，评估miR-21与PTEN的靶点关系。然后进行视网膜组织中miR-21、PTEN和PI 3 K/Akt/VEGF信号通路相关基因的表达鉴定。为了评估miR-21在DR中的贡献作用，用miR-21的模拟物或抑制剂或siRNA-PTEN转染RVEC，随后检测PTEN和PI 3 K/Akt/VEGF相关基因的表达，以及测量细胞活力、细胞周期和凋亡。DR大鼠视网膜组织中miR-21和PI 3 K/Akt/VEGF相关基因表达增加，沿着PTEN表达减少。PTEN被miR-21靶向并负调控，而PI 3 K/Akt/VEGF信号通路被miR-21激活。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。总之，我们的研究结果表明，miR-21过表达可能通过抑制PTEN表达激活PI 3 K/Akt/VEGF信号通路来刺激DR大鼠RVEC活力和血管生成，突出了miR-21作为DR治疗靶点的潜力。
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.