RETRACTED ARTICLE: Mst1 facilitates hyperglycemia-induced retinal pigmented epithelial cell apoptosis by evoking mitochondrial stress and activating the Smad2 signaling pathway

Abstract

Hyperglycemia induces retinal pigmented epithelial cell apoptosis and mitochondrial stress via poorly understood mechanisms. The goal of our current study is to explore whether mammalian sterile 20-like kinase 1 (Mst1) is involved in the pathogenesis of hyperglycemia-mediated retinal pigmented epithelial cell apoptosis by triggering mitochondrial abnormalities and activating the Smad2 signaling pathway. Retinal pigmented epithelial ARPE-19 cells were presented with a high-glucose challenge in vitro. Cell viability and apoptosis were measured via western blotting, ELISAs, and immunofluorescence assays. Mitochondrial function was detected via JC-1 staining, mitochondrial ROS flow cytometry, western blotting, and ELISAs. Loss-and gainof-function assays were performed via cell transfection and transduction with Mst1 siRNA and Smad2 adenovirus, respectively. The results indicated that hyperglycemia treatment upregulated the levels of Mst1, an effect that was accompanied by an increase in ARPE-19 cell apoptosis. Loss of Mst1 attenuated hyperglycemia-induced cell apoptosis, and this effect seemed to be associated with mitochondrial protection. In response to hyperglycemia stimulus, mitochondrial stress was noted in ARPE-19 cells, including mitochondrial ROS overproduction, mitochondrial respiratory metabolism dysfunction, mitochondrial fission/fusion imbalance, and mitochondrial apoptosis activation. Further, we provided evidence to support the crucial role played by Smad2 in promoting Mst1-mediated cell apoptosis and mitochondrial stress. Overexpression of Smad2 abrogated the beneficial effects of Mst1 deletion on ARPE-19 cell viability and mitochondrial protection. Altogether, our results identified Mst1 as a novel mediator controlling the fate of retinal pigmented epithelial cells and mitochondrial homeostasis via the Smad2 signaling pathway. Based on this finding, strategies to repress Mst1 upregulation and block Smad2 activation are vital to alleviate hyperglycemia-mediated retinal pigmented epithelial cell damage.

Retraction Note: Sirtuin 3 inhibition induces mitochondrial stress in tongue cancer by targeting mitochondrial fission and the JNK-Fis1 biological axis

“…The Editor-in-Chief has retracted this article (Zhou et al 2019) because of significant overlap was detected with text and figures in articles submitted and published within a close time frame. Specifically, there is text overlap with an article by different authors (Wei et al 2019) published earlier.…”

Influential Impact of Diabetes and Hyperlipoidemia Patients before and after Moderate Table Tennis Exercise

“…Keep a normal life. Observed fasting blood glucose FPG after 3 months, 2hPG after 2h, serum total cholesterol TC, triglyceride TG, high-density lipoprotein cholesterol, LDL-C level, evaluation criteria [8]: significant, TC decreased to normal or growth is greater than or equal to 20%, TG decreased to normal or decreased is greater than or equal to 40%, LDL-C decreased to normal or growth is greater than or equal to 20%, HDL-C rose to normal or is greater than or equal to 0.157mmolL-1; effective, TC decreased by 10%~20%, TG Decreased by 20%~40%, LDL-C decreased by 10%~20%, HDL-C increased by 0.130~0.157mmolL-1; invalid, did not reach effective standard; deterioration, TC increased ≥10%, TG growth is greater than or equal to 10%, HDL -C growth is greater than or equal to 0.130 mmol L-1, and LDL-C exceeded the normal limit.…”

“…Among them, exercise therapy is a method of exercise biology, which is divided into biomechanics and related neurodevelopmental directions, which can effectively improve the physical and functional effects of the body and other aspects. Treatments with strength and response as the main factors are mainly used in medicine [7][8]. In ancient times, there were some books describing the treatment of diabetes through exercise.…”