Wang Mingliang, Zheng Huifen, Zhou Xianbo, Zhang Jiwei, Shao Guanghui
Department of Ophthalmology, Hangzhou Lin'an District People's Hospital, Hangzhou City, People's Republic of China.
Department of Ophthalmology, Dongying Shengli Hospital of Traditional Chinese Medicine, Dongying City, People's Republic of China.
Anim Cells Syst (Seoul). 2020 Sep 10;24(5):275-281. doi: 10.1080/19768354.2020.1816580.
Diabetic retinopathy (DR) is a primary complication of diabetes mellitus. DR can cause severe vision loss for patients. miR-122 is elevated in DR patients, while its role in DR is unclear. Hence, the purpose of this study was to analyze the effect of miR-122 on the function of high glucose-induced REC cells and the underlying molecular mechanisms. In this study, our results revealed that miR-122 was up-regulated in high glucose-induced human retinal pigment epithelial cells (ARPE-19). High glucose decreased the cell viability of ARPE-19 cells, which was then restored by miR-122 knockdown. In addition, miR-122 knockdown suppressed apoptosis of high glucose-induced ARPE-19 cells. High glucose also inhibited B-cell lymphoma-2 (Bcl-2) level and increased cleaved caspase-3 level in ARPE-19 cells, which were reversed by miR-122 knockdown. Tissue inhibitor of metalloproteinases-3 (TIMP3) was a direct target of miR-122. TIMP3 was decreased in high glucose-induced ARPE-19 cells, and the decrease was abrogated by miR-122 knockdown. In addition, the effects of miR-122 overexpression in cell viability and apoptosis of high glucose-induced ARPE-19 were abolished by overexpression of TIMP3. In conclusion, the effect and mechanism of miR-122 on high glucose-induced ARPE-19 cells were demonstrated for the first time. miR-122 promoted diabetic retinopathy through targeting TIMP3, making miR-122 a promising target for diabetic retinopathy therapy.
糖尿病视网膜病变（DR）是糖尿病的主要并发症。DR可导致患者严重视力丧失。miR-122在DR患者中升高，但其在DR中的作用尚不清楚。因此，本研究的目的是分析miR-122对高糖诱导的视网膜色素上皮细胞（REC）功能的影响及其潜在分子机制。在本研究中，我们的结果显示，在高糖诱导的人视网膜色素上皮细胞（ARPE-19）中miR-122上调。高糖降低了ARPE-19细胞的活力，而miR-122敲低可使其恢复。此外，miR-122敲低抑制了高糖诱导的ARPE-19细胞凋亡。高糖还抑制了ARPE-19细胞中B细胞淋巴瘤-2（Bcl-2）的水平并增加了裂解的半胱天冬酶-3的水平，而miR-122敲低可使其逆转。金属蛋白酶组织抑制剂-3（TIMP3）是miR-122的直接靶点。在高糖诱导的ARPE-19细胞中TIMP3降低，而miR-122敲低可消除这种降低。此外，TIMP3的过表达消除了miR-122过表达对高糖诱导的ARPE-19细胞活力和凋亡的影响。总之，首次证明了miR-122对高糖诱导的ARPE-19细胞的作用及机制。miR-122通过靶向TIMP3促进糖尿病视网膜病变，使miR-122成为糖尿病视网膜病变治疗的一个有前景的靶点。
