Effects of microRNA‑217 on high glucose‑induced inflammation and apoptosis of human retinal pigment epithelial cells (ARPE‑19) and its underlying mechanism

Xiao,Hongxia; Liu,Zhen

doi:10.3892/mmr.2019.10778

Effects of microRNA‑217 on high glucose‑induced inflammation and apoptosis of human retinal pigment epithelial cells (ARPE‑19) and its underlying mechanism

Authors:
- Hongxia Xiao
- Zhen Liu
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Affiliations: Department of Ophthalmology, Jing Men No. 2 People's Hospital, Jingmen, Hubei 448000, P.R. China, Department of Ophthalmology, Chongqing Aier Eye Hospital, Chongqing 400020, P.R. China
Published online on: October 30, 2019 https://doi.org/10.3892/mmr.2019.10778
Pages: 5125-5133
Copyright: © Xiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Diabetic retinopathy is a major complication of diabetes. Increasing evidence has indicated that microRNAs (miRs) serves an important role in diabetic retinopathy. However, the expression and mechanism of miR‑217 in high glucose‑induced human retinal pigment epithelial cells ARPE‑19 is still unclear. Therefore, the aim of this study was to investigate the role of miR‑217 in high glucose‑induced retinal epithelial cell damage, and further to explore the molecular mechanisms. In our study, we found that compared with control group, miR‑217 was upregulated in high glucose‑induced ARPE‑19 cells. In addition, TargetScan and a dual‑luciferase reporter gene assay showed that Sirtuin 1 (SIRT1) was a direct target of miR‑217. Then, we performed reverse transcription‑quantitative polymerase chain reaction assay and western blot assay to explore the expression of SIRT1 in high glucose‑induced ARPE‑19 cells. Our results demonstrated that SIRT1 was downregulated at the mRNA and protein levels in high glucose‑induced ARPE‑19 cells. Then, ARPE‑19 cells were transfected with inhibitor control, miR‑217 inhibitor or miR‑217 inhibitor + SIRT1‑small interfering RNA for 6 h, and then the cells were treated with 50 mM D‑glucose for 24 h. We then investigated the effects of miR‑217 inhibitor on ARPE‑19 cell viability and apoptosis. An MTT assay revealed that miR‑217 inhibitor significantly increased the viability and decreased the apoptosis of high glucose‑induced ARPE‑19 cells. ELISA indicated that miR‑217 inhibitor significantly reduced the expression of inflammatory factors, such as interleukin (IL)‑1β, tumor necrosis factor‑α, and IL‑6 in high glucose‑treated ARPE‑19 cells. Additionally, a western blot assay demonstrated that miR‑217 inhibitor suppressed the expression of p‑p65. The effects of miR‑217 inhibitor on high glucose‑treated ARPE‑19 cells were significantly reversed by the silencing the SIRT1 gene. Therefore, our findings suggested that miR‑217 inhibitor protected against retinal epithelial cell damage caused by high glucose via targeting SIRT1, thereby playing a protective role in diabetic retinopathy. Targeting miR‑217 may have therapeutic potential in the treatment of diabetic retinopathy.

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