MiR‐455‐5p ameliorates HG‐induced apoptosis, oxidative stress and inflammatory via targeting SOCS3 in retinal pigment epithelial cells

Abstract

Diabetic retinopathy (DR) remains the leading cause of blindness in adults with diabetes mellitus. Numerous microRNAs (miRNAs) have been identified to modulate the pathogenesis of DR. The main purpose of this study was to evaluate the potential roles of miR-455-5p in high glucose (HG)-treated retinal pigment epithelial (RPE) cells and underlying mechanisms. Our present investigation discovered that the expression of miR-455-5p was apparently downregulated in ARPE-19 cells stimulated with HG. In addition, forced expression of miR-455-5p markedly enhanced cell viability and restrained HG-induced apoptosis accompanied by decreased BCL2-associated X protein (Bax)/B-cell leukemia/lymphoma 2 (Bcl-2) ratio and expression of apoptotic marker cleaved caspase-3 during HG challenged. Subsequently, augmentation of miR-455-5p remarkably alleviated HG-triggered oxidative stress injury as reflected by decreased the production of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) content as well as NADPH oxidase 4 expression, concomitant with enhanced the activities of superoxide dismutase, catalase, and GPX stimulated with HG. Furthermore, enforced expression of miR-455-5p effectively ameliorated HG-stimulated inflammatory response as exemplified by repressing the secretion of inflammatory cytokines interleukin 1β (IL-1β), IL-6, and tumour necrosis factor-α in ARPE-19 cells challenged by HG. Most importantly, we successfully identified suppressor of cytokine signaling 3 (SOCS3) as a direct target gene of miR-455-5p, and miR-455-5p negatively regulated the expression of SOCS3. Mechanistically, restoration of SOCS3 abrogated the beneficial effects of miR-455-5p on apoptosis, accumulation of ROS, and inflammatory factors production in response to HG. Taken together, these findings demonstrated that miR-455-5p relieved HG-induced damage through repressing apoptosis, oxidant stress, and inflammatory response by targeting SOCS3. The study gives evidence that miR-455-5p may serve as a new potential therapeutic agent for DR treatment. K E Y W O R D S apoptosis, diabetic retinopathy, inflammatory response, MiR-455-5p, oxidative stress, SOCS3

Comparative efficacy and safety of anti-vascular endothelial growth factor regimens for neovascular age-related macular degeneration: systematic review and Bayesian network meta-analysis

“…CRT change may also implicate the morphological disruption and dysfunction of the inner or outer blood-retinal barrier during the development of disease. [54][55][56][57][58] There was no significant difference between pegaptanib every 6 weeks and the sham injection group in terms of efficacy and safety, which differs from the results of the VISION trials. 17,59 This finding, together with National Institute for Health and Care Excellence (NICE) guidance, indicated that pegaptanib is not recommended for the treatment of nAMD.…”

“…CRT change may also implicate the morphological disruption and dysfunction of the inner or outer blood-retinal barrier during the development of disease. 54 – 58 …”

The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress

“…Considering retinal pigment epithelial (RPE) cells, miR-455-5p ameliorated OxS and inflammation triggered by HG, as shown by the increased activity of antioxidant defense genes (SOD, CAT, GPx), reduced ROS production, expression of NOX4 and proinflammatory cytokines. This beneficial impact was proven to be mediated by the direct regulation of previously mentioned SOCS3 [255]. In another study, quercetin elicited the upregulation of miR-29b in HG-exposed RPE cells, thus leading to amelioration of ROS production due to miR-29b-dependent beneficial regulation of PTEN/AKT and NF-κ pathways [256].…”

MicroRNAs: Potential Targets in Diabetic Retinopathy

“…Suppressor of cytokine signaling 3 (SOCS3) is a direct target gene of miR-455-5p and negatively regulated by miR-455-5p. The study showed that augmentation of miR-455-5p remarkably alleviated HG-triggered oxidative stress injury as reflected by decreased the production of intracellular ROS and malondialdehyde (MDA) content as well as NADPH oxidase 4 expression, concomitant with enhanced the activities of superoxide dismutase, catalase, and GPX [48]. That is to say, miR-455-5p has antioxidant activity and could be as a new potential therapeutic agent for DR treatment.…”