Yuan Shuyi, He Guanghui, Li Lihua
Department of Optometry Center, Tianjin Eye Hospital Tianjin 300022, China.
Department of Vitreoretinopathy, Tianjin Eye Hospital Tianjin 300022, China.
Am J Transl Res. 2021 Mar 15;13(3):1505-1515. eCollection 2021.
This study was aimed to determine the role of has-miR-155 and E2F2 on corneal endothelial cells. Real-time quantitative PCR and Western blot assays were carried out to determine the levels of has-miR-155 and E2F2, and Flow cytometry assay was conducted to detect cell cycle. In addition, Targetscan7.2 was adopted to analyze the internal connection between hsa-miR-155 and E2F2, and a dual luciferase reporter gene assay to determine predicted site between has-miR-155 and E2F2. Increased hsa-miR-155 resulted in decreased E2F2, while decreased hsa-miR-155 increased the level of E2F2. In addition, both increased hsa-miR-155 and decreased E2F2 led to an increase in S-phase cells and a decrease in G1-phase cells. Also, they induced an increase in the activity of barrier-related proteins MLCK and ZO-1, an up-regulation of Cyclin D1 and Cyclin E1, and a down-regulation of apoptosis proteins (Caspase 3/Bax/Bim/Bid) whereas decreased hsa-miR-155 led to an opposite change in cells, and decreased E2F2 could offset cell changes caused by increased has-miR-155. In conclusion, Has-miR-155 regulates the cell cycle of corneal endothelial cells and improves their barrier function by down regulating E2F2.
本研究旨在确定has-miR-155和E2F2在角膜内皮细胞中的作用。采用实时定量PCR和蛋白质免疫印迹法检测has-miR-155和E2F2的水平,通过流式细胞术检测细胞周期。此外,采用Targetscan7.2分析hsa-miR-155与E2F2之间的内在联系,并通过双荧光素酶报告基因检测法确定has-miR-155与E2F2之间的预测位点。hsa-miR-155升高导致E2F2降低,而hsa-miR-155降低则使E2F2水平升高。此外,hsa-miR-155升高和E2F2降低均导致S期细胞增加,G1期细胞减少。它们还诱导屏障相关蛋白MLCK和ZO-1的活性增加,细胞周期蛋白D1和细胞周期蛋白E1上调,凋亡蛋白(半胱天冬酶3/ Bax / Bim / Bid)下调,而hsa-miR-155降低导致细胞出现相反变化,E2F2降低可抵消hsa-miR-155升高引起的细胞变化。总之,Has-miR-155通过下调E2F2来调节角膜内皮细胞的细胞周期并改善其屏障功能。