Affiliation:
1. Department of Ophthalmology, YanTaiShan Hospital, Yantai, China
2. School of Pharmacy, Yantai University, Yantai, China
Abstract
To explore the potential function of tricin in diabetic retinopathy (DR) and investigate whether Sestrin2 is closely involved in DR. A single intraperitoneal injection of streptozotocin-induced diabetes model in Sprague-Dawley rats and a high glucose-induced retinal epithelial cell model in ARPE-19 cells were established. The retinas were removed and examined by hematoxylin-eosin (HE) staining and dihydroethidium (DHE) staining. The proliferation ability and reactive oxygen species (ROS) level of ARPE-19 cells were detected by 5-ethynyl-2′-deoxyuridine (EdU) and flow cytometry. Then, the content of superoxide dismutase (SOD), malonaldehyde (MDA), and glutathione peroxidase (GSH-Px) in serum or cell supernatant was tested using enzyme linked immunosorbent assay (ELISA). In addition, the expression of Sestrin2, nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), platelet endothelial cell adhesion molecule-1 (CD31), and vascular endothelial growth factor receptor 2 (VEGFR2) in retina tissue or ARPE-19 cells were validated through western blot and immunofluorescence assays. With the increase of MDA and ROS concentration, Sestrin2 expression was downregulated significantly, and Nrf2 and HO-1 expression was also reduced in retina tissue or ARPE-19 cells of model group, whereas CD31 and VEGFR2 expression was upregulated. However, tricin ameliorated the oxidative stress and angiogenesis and rectified the abnormal expression of Sestrin2/Nrf2 in diabetic retinopathy. Further mechanistic studies showed that silence Sestrin2 reduced the protective effect of tricin on ARPE-19 cells, as well as abolished its regulating effect on the Nrf2 pathway. These results suggested that tricin inhibits oxidative stress and angiogenesis in retinal epithelial cells of DR rats via reinforcing Sestrin2/Nrf2 signaling.
Subject
Health, Toxicology and Mutagenesis,Toxicology,General Medicine
Cited by
6 articles.
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