Astragalus polysaccharides suppresses high glucose-induced metabolic memory in retinal pigment epithelial cells through inhibiting mitochondrial dysfunction-induced apoptosis by regulating miR-195

Abstract

Background Metabolic memory contributes to the development of diabetic retinopathy (DR), which is the complication of diabetes. But it’s still unknown how to prevent the metabolic memory to treat the DR. In our study, we want to examine the function of Astragalus polysaccharides (APS) in the metabolic memory of retinal pigment epithelium (RPE) pretreated with high glucose (HG). Methods ARPE-19 and PRPE cells were exposed to HG followed by normal glucose (NG) treatment with or without APS. QPCR was used to examine the levels of miR-195 and Bcl-2. MDA and SOD detection assays were used to examine the oxidative stress level. Western blotting and immunostaining were applied to detect the protein level of mitochondrial damage and apoptotic signaling pathway. Flow cytometry and TUNEL staining were used to analyze cell apoptosis. Luciferase assay was used to examine the direct target of miR-195. Results APS treatment significantly decreased the expression of miR-195, while increased the expression of Bcl-2 with optimized dosages which were induced by HG treatment, even after replacing the HG with NG. And we found Bcl-2 was the direct target of miR-195. APS alleviated the oxidative stress, mitochondrial damage and cell apoptosis induced by HG and HG + NG treatments in RPE cells via regulating miR-195. Furthermore, we found overexpression of miR-195 abolished the alleviated effects of APS on the HG-treated RPE cells. Conclusions APS suppressed high glucose-induced metabolic memory in retinal pigment epithelial cells through inhibiting mitochondrial dysfunction-induced apoptosis by regulating miR-195.

lncRNA FGD5 antisense RNA 1 upregulates RORA to suppress hypoxic injury of human cardiomyocyte cells by inhibiting oxidative stress and apoptosis via miR‑195

“…Furthermore, it was discovered in the present study that mir-195 expression levels were highly induced by hypoxic stress, which is consistent with the effects of H 2 o 2 stimulation or high glucose stress on mir-195 regulation (39). By contrast, mir-195 downregulation was coupled with a diminishing effect on Mda and promoting effect on SOD; this was consistent with results reported by Liu et al (40).…”

Astragalus polysaccharides attenuate pulmonary�fibrosis by inhibiting the epithelial-mesenchymal�transition and NF-κB pathway activation

“…P revious studies repor ted the antitumor (28), anti-diabetic (29), antioxidant and immunomodulatory properties of APS (30,31). Several studies demonstrated that Astragalus has strong anti-fibrotic activities (12,15).…”

The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress

“…Injury and ROS generation induced by HG were also associated with downexpression of miR-26a and possibly through enhancement of signaling via ERK Wnt/β-catenin pathways [260]. Another miRNA, miR-195, was upregulated in the course of diabetic retinopathy leading to aggravated OxS, mitochondrial damage and apoptosis of RPE cells via Bcl-2 targeting [261]. miR-195 was also indicated to be increased in retinas of diabetic mice while directly targeting 3 UTR of mitofusin-2 (MFN-2) [262].…”