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LncRNA FLG-AS1 Mitigates Diabetic Retinopathy by Regulating Retinal Epithelial Cell Inflammation, Oxidative Stress, and Apoptosis via miR-380-3p/SOCS6 Axis

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Abstract

The objective of this study is to investigate lncRNA FLG-AS1-mediated miR-380-3p/SOCS6 axis in inflammation, oxidative stress, and apoptosis of retinal epithelial cells in diabetic retinopathy (DR). Fasting blood was collected from 60 DR patients and 60 healthy controls. The Pearson correlation was used to analyze the correlation between the expression levels of FLG-AS1 and miR-380-3p in DR patients. qRT-PCR and/or Western blotting were used to detect the expression of FLG-AS1, miR-380-3p, and SOCS6. After gain of function of FLG-AS1 or SOCS6 or loss of function of miR-380-3p, high glucose (HG)–treated human retinal pigment epithelial ARPE-19 cells were subjected to TUNEL assessment of apoptosis. ELISA was performed to detect the expression levels of IL-1β, IL-6, and TNF-α in cell culture supernatant. DCFH-DA was used to detect the level of ROS in the cells. MDA and SOD assay kits were used to measure the activity of MDA and SOD in the cells. Dual-luciferase reporter assay was performed to verify the binding between miR-380-3p and FLG-AS1 or between miR-380-3p and SOCS6. Streptozotocin injections were used to induce diabetes in rats which were injected with FLG-AS1 overexpression lentiviral vectors in the eye. Twenty weeks later, retinal tissue was isolated and stained with hematoxylin–eosin or TUNEL. Compared to that in healthy controls, FLG-AS1 expression decreased 2.5-fold and miR-380-3p expression increased 2.6-fold in the serum of DR patients. The expression levels of FLG-AS1 and miR-380-3p were negatively correlated in DR patients (r = −0.3772, P = 0.003). Overexpression of FLG-AS1 reduced inflammation, oxidative stress, and apoptosis of HG-treated ARPE-19 cells and alleviated retinal injury in diabetic rats. FLG-AS1 promoted the expression of SOCS6 by targeting miR-380-3p. Inhibition of miR-380-3p or overexpression of SOCS6 reduced inflammation, oxidative stress, and apoptosis of HG-treated ARPE-19 cells. FLG-AS1 mitigates DR by regulating retinal epithelial cell inflammation, oxidative stress, and apoptosis via the miR-380-3p/SOCS6 axis.

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Availability of Data and Materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of ophthalmology, The First Affiliated Hospital of Nanchang Medical college, Jiangxi Provincial People’s Hospital, No. 92, Aiguo Road, Nanchang, Jiangxi, 330006, People’s Republic of China

    Rong Luo, Lan Li, Fan Xiao & Jinsong Fu

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  1. Rong Luo
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  3. Fan Xiao
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Contributions

LR conceived the ideas. LR designed the experiments. LL, XF, and FJS performed the experiments. LL, XF, and FJS analyzed the data. LR and LL provided critical materials. XF and FJS wrote the manuscript. LR supervised the study. All the authors have read and approved the final version for publication.

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Correspondence to Rong Luo.

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All animal experiments in this study were carried out with the approval from the Animal Care and Use Committee of Jiangxi Provincial People’s Hospital Affiliated to Nanchang University.

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The authors declare no competing interests.

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Luo, R., Li, L., Xiao, F. et al. LncRNA FLG-AS1 Mitigates Diabetic Retinopathy by Regulating Retinal Epithelial Cell Inflammation, Oxidative Stress, and Apoptosis via miR-380-3p/SOCS6 Axis. Inflammation 45, 1936–1949 (2022). https://doi.org/10.1007/s10753-022-01665-6

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  • DOI: https://doi.org/10.1007/s10753-022-01665-6

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