Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, 10540, Thailand.
Pediatric Translational Research Unit, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand; Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand.
Biomed Pharmacother. 2020 Nov;131:110655. doi: 10.1016/j.biopha.2020.110655. Epub 2020 Aug 24.
Disturbance of endoplasmic reticulum (ER) homeostasis triggered by the accumulation of unfolded proteins and advanced glycation end-products (AGEs) plays a major role in pathophysiology of diabetic nephropathy. Activation of receptor for AGEs (RAGE) stimulates NADPH oxidase-mediated reactive oxygen species (ROS) production, leading to ER stress, inflammation, glomerular hypertrophy, podocyte injury, and renal fibrosis. A growing body of evidence indicates that non-coding RNAs (ncRNAs) could rescue ER stress and renal inflammation by the epigenetic modification. This review summarizes ncRNA regulation in AGE/RAGE signaling-mediated ER stress, and discusses the opportunities and challenges of ncRNA-loaded extracellular vesicle therapy in diabetic nephropathy.
内质网 (ER) 稳态的紊乱是由未折叠蛋白和晚期糖基化终产物 (AGEs) 的积累触发的，这在糖尿病肾病的病理生理学中起着主要作用。AGEs 受体 (RAGE) 的激活刺激 NADPH 氧化酶介导的活性氧 (ROS) 产生，导致 ER 应激、炎症、肾小球肥大、足细胞损伤和肾纤维化。越来越多的证据表明，非编码 RNA (ncRNA) 可以通过表观遗传修饰来挽救 ER 应激和肾脏炎症。本综述总结了 ncRNA 在 AGE/RAGE 信号转导介导的 ER 应激中的调控作用，并讨论了 ncRNA 负载的细胞外囊泡治疗糖尿病肾病的机遇和挑战。
