A Novel Mechanism of Regulation for Exosome Secretion in the Diabetic Kidney.

Abstract

Exosomes are nano-sized membrane vesicles generated by inward invagination of the endosomal membrane and released by the fusion of multivesicular bodies (MVB) with plasma membrane in various cell types (Fig. 1) (1). Once released, exosomes have diverse activities such as transmitting signals and biomolecules to neighboring or distant recipient cells and regulating the extracellular environment (2). Secreted exosomes have been shown to mediate intercellular communication among kidney cells and may play a key role in the pathogenesis of diabetic kidney disease (DKD) (3,4). Thus, it is important to understand the role and mechanisms of exosome secretion in the diabetic kidneys. Figure 1 Schematic representation of exosome biogenesis, transport, and secretion. Briefly, the exosome generation consists of three steps: biogenesis, intracellular transport, and release. A : Biogenesis. An inward invagination of the plasma membrane or membrane fractions from the trans -Golgi network (TGN) form early endosomes, which later mature into late endosomes/MVBs via inward budding of the endosomal membrane as intraluminal vesicles (conventional mediators include endosome sorting complex required for transport [ESCRT], ceramide/neutral sphingomyelinase 2 [nSMase2], tetraspanins, ALG-2 interacting protein X [ALIX], etc.). B : MVB trafficking. The fate of MVBs may vary and depend on molecules and effectors mediated (e.g., RAB27A/B fuses with the plasma membrane, RAB7/11 fuses to lysosome/autophagosome, etc.). C : Exosome release. The membrane of MVB fuses with the plasma membrane, which …