Abstract
Objective: MicroRNA-218 (miR-218) critical for preventing the progression of numerous diseases, including diseases of the retinal pigment epithelium (RPE). However, the mechanism by which miR-218 regulates the PRE in humans remains largely unknown. Our study investigated the effects of glucose-induced miR-218 expression on human RPE cells (ARPE-19), as well as its targeted regulatory effect.Methods: The levels of miR-218 and runt-related transcription factor 2 (RUNX2) expression were investigated by RT-qPCR or Western blot assays. Cell viability and apoptosis were assessed by CCK-8 assays, flow cytometry, and Hoechst staining. A luciferase reporter assay was performed to determine whether Runx2 is a target gene of miR-218.Results: Our results showed that glucose up-regulated miR-218 expression, suppressed proliferation, and induced the apoptosis of ARPE-19 cells. We verified that miR-218 could inhibit the proliferation and facilitate the apoptosis of ARPE-19 cells, while inhibition of miR-218 expression produced the opposite effects. In terms of mechanism, we demonstrated that RUNX2 was a direct target of miR-218. Functional experiments showed that Runx2 served as a miR-218 target to help inhibit the proliferation and induction of apoptosis in ARPE-19 cells.Conclusion: Our findings suggest the miR-218/Runx2 axis as a potential target for treating diabetic retinopathy (DR).
Highlights
Diabetic retinopathy (DR) is a series of fundus lesions caused by abnormal retinal circulation resulting from aberrant glucose metabolism in diabetic patients [1]
Hoechst staining and flow cytometry analyses revealed that ARPE 19 cells treated with glucose had significantly increased rates of apoptosis when compared with control cells (Figure 1C,D)
These results suggested that glucose inhibited the proliferation and promoted the apoptosis of ARPE-19 cells in dose dependent manners, which might be related to changes in miR-218 expression
Summary
Diabetic retinopathy (DR) is a series of fundus lesions caused by abnormal retinal circulation resulting from aberrant glucose metabolism in diabetic patients [1]. In the early stage of DR, the basal membrane of capillary endothelial cells is thickened, peripheral cells are lost, and the automatic regulatory function of capillaries is decompensated. DR is one of the most common causes of preventable blindness among working-age people, and the incidence of retinopathy in diabetic patients with a course > 10 years exceeds 50% [5]. DR can be divided into early stage and late stage DR based on its severity; proliferative diabetic retinopathy (PDR) represents the advanced stage, which can severely affect the vision of patients with diabetes [6,7]. It is of great importance to study its pathogenesis with the goal of preventing and treating DR, and finding new therapeutic molecular targets
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