AGE/RAGE signaling-mediated endoplasmic reticulum stress and future prospects in non-coding RNA therapeutics for diabetic nephropathy

Abstract

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.

Keywords: AGE/RAGE/Nox signaling; Diabetic nephropathy; ER stress; Extracellular vesicle delivery; RNA-based drugs.