RETRACTED ARTICLE: Salidroside alleviates high-glucose-induced injury in retinal pigment epithelial cell line ARPE-19 by down-regulation of miR-138

Abstract

Diabetic retinopathy (DR) is a complication of diabetes leading cause of blindness in adults. Salidroside (SAL) is a main ingredient from Rhodiola rosea L., has been reported to have a beneficial protection on vascular function. However, whether SAL is a suitable treatment for DR remains unreported. The study aimed to investigate the effect of SAL on high-glucose (HG)-induced injury in ARPE-19 cells. ARPE-19 cells were managed with diverse concentrations of glucose, and constructed a model of HG-induced ARPE-19 cells injury. Then, SAL was employed to stimulate ARPE-19 cells, and cell viability, apoptosis, apoptosis-associated factors, the pro-inflammatory cytokines, and ROS levels were determined. The correlation between miR-138 and SIRT1 was predicated by bioinformatics software of TargetScan (http://www.targetscan.org/) and Dual luciferase reporter assay. MiR-138 mimic, inhibitor and NCs were transfected into ARPE-19 cells, and the impacts of miR-138 on HG-induced cell injury were investigated. PI3K/AKT and AMPK signalling pathways were examined to explore the underlying mechanism. The results disclosed that HG inhibited cell viability, promoted apoptosis, up-regulated IL-6 and TNF-α, as well as increased ROS level in ARPE-19 cells. But, SAL obviously alleviated HG-induced ARPE-19 cells injury. Repressed miR-138 was triggered by SAL, and SIRT1 was predicated as a direct target of miR-138. Overexpressed miR-138 declined the protective effect of SAL on HG-injured ARPE-19 cells. Besides, SAL activated PI3K/AKT and AMPK pathways by adjusting miR-138. In conclusions, SAL flattened HG-induced injury in ARPE-19 cells by repression of miR-138 and activating PI3K/ AKT and AMPK pathways.

The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress

“…On the other hand, SIRT1 induces miR-182, a direct regulator of NOX4, so as to protect from diabetic keratopathy [187]. SIRT1 was also recently found to be regulated by miR-138 in HG-induced OxS-affected retinal cells [188]. Retinal cells affected by HG were also found to express downregulation of lncRNA small nucleolar RNA host gene 7 (SNHG7), leading to elevation of miR-543 and its direct targeting of SIRT1 and decrease of vascular endothelial growth factor (VEGF) [189].…”

Elucidating the mechanism of action of alpha-1-antitrypsin using retinal pigment epithelium cells exposed to high glucose. Potential use in diabetic retinopathy

“…ARPE-19 cells exposed to high glucose (Retinal Pigment Epithelial immortalized cell line derived from Amy Aotaki-Keen eyes) is a widely used in vitro model of diabetic retinopathy. Exposing cells to high glucose concentrations (from 16.5 mM to 33 mM) with 10% fetal bovine serum mimics diabetic retinopathy milieu [19][20][21][22][23].…”

SIRT3 deficiency increases mitochondrial oxidative stress and promotes migration of retinal pigment epithelial cells

“…Investigations have explored the effect of high glucose, a key underlying factor in initiating and progressing the major complications of diabetes, including DR, on RPE cell function. 7–11 As a significant energy source for retinal metabolism, glucose is transported largely via RPE cells, 12–14 which provide 60%–80% of retinal glucose through their high-capacity distribution system. 15 Meanwhile, RPE cells are highly susceptible to high concentrations of glucose, and how hyperglycemia impacts RPE cell function remains a question of great interest.…”