Abstract
Purpose: To explore the protective effects of artemisinin (Art) against diabetic retinopathy (DR) and the probable mechanism of action.Methods: MIO-M1 cells were treated with high glucose (HG) and Art, and the cells’ proliferative ability was determined using cell counting kit-8 (CCK-8) and 5-ethynyl-2’-deoxyuridine (EdU) assay. The relative levels of inflammatory factors in the culture medium of MIO-M1 cells were determined by enzyme-linked immunosorbent assay (ELISA). while the expression levels of CASC2, miR-155 and Sirtuin1 (SIRT1) in MIO-M1 cells were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Interaction of Art with the cell target was assessed using dual-luciferase reporter assay. The role of the CASC2/miR-155/SIRT1 axis in Art-induced protection against the proliferation and inflammation of MIO-M1 cells was evaluated.Results: HG induced elevated proliferation of MIO-M1 cells and production of inflammatory factors, but these effects were countered by Art treatment (p < 0.05). CASC2 and SIRT1 were upregulated, while miR-155 was downregulated in HG-treated MIO-M1 cells; changes in their expressions remained the same following Art treatment. CASC2/miR-155/SIRT1 axis was responsible for the ameliorative effect of Art on HG-treated MIO-M1 cells.Conclusion: Artemisinin treatment inhibits cell activation and production of pro-inflammatory cytokines in HG-induced MIO-M1 cells via CASC2/miR-155/SIRT1 axis. Thus, artemisinin has potentials for development into a therapeutic agent for the management of diabetic retinopathy.
Highlights
Diabetic retinopathy (DR) is a common diabetic microvascular complication which is the leading cause of blindness in working-age people in developed countries [1]
high glucose (HG) induction markedly enhanced cell viability and ethynyl-2’- deoxyuridine (EdU)-positive percentage in MIO-M1 cells, which were reduced after Art treatment
CASC2 was downregulated in HG-induced MIOM1 cells, which was reversed by Art treatment (Figure 2 A)
Summary
Diabetic retinopathy (DR) is a common diabetic microvascular complication which is the leading cause of blindness in working-age people in developed countries [1]. Artemisinin (Art) is the first-line drug for the treatment of malaria because of its rapid toxicity to Plasmodium [5]. Artemisinin extract is able to obviously decrease blood sugar and blood lipid levels in diabetic rats, which protects the liver and kidney functions [6]. The antiinflammatory effect of Art has been reported. They exert an anti-angiogenic effect on rheumatoid arthritis by downregulating angiogenesis-associated genes, including MMP2, MMP-9, VEGF and HIF-1α [7]. Wei et al [8] reported that Art is of significance in the development of DR
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