Salidroside Prevents Hypoxia-Induced Human Retinal Microvascular Endothelial Cell Damage Via miR-138/ROBO4 Axis.
Salidroside Prevents Hypoxia-Induced Human Retinal Microvascular Endothelial Cell Damage Via miR-138/ROBO4 Axis.
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DOI：
10.1167/iovs.62.9.25
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发表时间：
2021-07-01
影响因子：
4.4
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Shi X;Dong N;Qiu Q;Li S;Zhang J
视网膜病变与视网膜微血管内皮细胞的损伤有关。红景天苷（SAL）是一种具有抗氧化和细胞保护特性的药用补充剂。我们推测SAL可能在视网膜病变中具有保护作用。本研究旨在探讨SAL在缺氧性视网膜微血管内皮细胞损伤中的作用及机制。在低氧条件下培养人视网膜微血管内皮细胞（HRMECs），诱导HRMECs损伤。采用细胞计数试剂盒、8，5-乙炔基-2 ′-脱氧尿苷（EdU）染色、流式细胞术、Western blotting和酶联免疫吸附试验研究SAL对HRMEC损伤的作用。使用定量逆转录聚合酶链反应或蛋白质印迹法检测MicroRNA（miR）-138、roundabout 4（ROBO 4）和磷酸肌醇3-激酶（PI 3 K）/蛋白激酶B（AKT）/哺乳动物雷帕霉素靶蛋白（mTOR）通路中的蛋白质。通过双荧光素酶报告基因分析和RNA免疫沉淀确定靶相关性。缺氧导致HRMEC增殖抑制、周期阻滞、凋亡、炎症反应和氧化应激。SAL可通过促进细胞增殖、减轻细胞周期阻滞、细胞凋亡、炎症反应和氧化应激来减轻缺氧引起的HRMEC损伤。缺氧可增强miR-138的表达，而SAL刺激可降低miR-138的表达。miR-138上调逆转SAL对缺氧诱导的HRMECs损伤的影响。通过miR-138靶向ROB 0 4。ROBO 4过表达减弱了miR-138在HRMEC损伤中的作用。缺氧条件下PI 3 K/AKT/mTOR通路失活，SAL通过降低miR-138增加PI 3 K/AKT/mTOR通路的活化。SAL通过调节miR-138/ROBO 4轴保护缺氧诱导的HRMEC损伤，表明SAL在视网膜病变中具有保护作用。
Retinopathies are associated with the injury of retinal microvascular endothelial cells. Salidroside (SAL) is a medicinal supplement that has antioxidative and cytoprotective properties. We hypothesized that SAL might have a protective function in retinopathies. This research aims to explore the function and mechanism of SAL in hypoxia-induced retinal microvascular endothelial cell injury. Human retinal microvascular endothelial cells (HRMECs) injury was induced by culturing under hypoxic condition. The function of SAL on HRMECs injury was investigated using cell counting kit-8, 5-ethynyl-2′-deoxyuridine (EdU) staining, flow cytometry, Western blotting, and enzyme linked immunosorbent assay. MicroRNA (miR)-138, roundabout 4 (ROBO4), and proteins in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways were examined using quantitative reverse transcription polymerase chain reaction or Western blotting. The target correlation was determined by dual-luciferase reporter analysis and RNA immunoprecipitation. Hypoxia resulted in proliferation inhibition, cycle arrest, apoptosis, inflammatory reaction, and oxidative stress in HRMECs. SAL attenuated hypoxia-induced HRMECs injury via increasing cell proliferation, and mitigating cycle arrest, apoptosis, inflammatory reaction, and oxidative stress. MiR-138 expression was enhanced by hypoxia, and decreased via SAL stimulation. MiR-138 upregulation reversed the influence of SAL on hypoxia-induced HRMECs injury. ROBO4 was targeted via miR-138. ROBO4 overexpression weakened the role of miR-138 in HRMECs injury. The PI3K/AKT/mTOR pathway was inactivated under hypoxic condition, and SAL increased the activation of PI3K/AKT/mTOR pathways by decreasing miR-138. SAL protected against hypoxia-induced HRMECs injury through regulating miR-138/ROBO4 axis, indicating the protective potential of SAL in retinopathies.
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