Abstract
Proteinuria is an independent risk factor for end-stage renal disease (ESRD) (Shankland, 2006). Recent studies highlighted the mechanisms of podocyte injury and implications for potential treatment strategies in proteinuric kidney diseases (Zhang et al., 2012). Reactive oxygen species (ROS) are cellular signals which are closely associated with the development and progression of glomerular sclerosis. NADPH oxidase is a district enzymatic source of cellular ROS production and prominently expressed in podocytes (Zhang et al., 2010). In the last decade, it has become evident that NADPH oxidase-derived ROS overproduction is a key trigger of podocyte injury, such as renin-angiotensin-aldosterone system activation (Whaley-Connell et al., 2006), epithelial-to-mesenchymal transition (Zhang et al., 2011), and inflammatory priming (Abais et al., 2013). This review focuses on the mechanism of NADPH oxidase-mediated ROS in podocyte injury under different pathophysiological conditions. In addition, we also reviewed the therapeutic perspectives of NADPH oxidase in kidney diseases related to podocyte injury.
Highlights
Chronic kidney disease (CKD) is a major public health problem worldwide
Recent studies show that insulin treatment increased the generation of H2O2, the surface expression of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, NOX4, and TRPC6 channels in cultured podocytes [22, 30]. These results suggest that NOX4 may play a role in insulin signaling via TRPC6 channels and may induce insulin resistance in podocytes in diabetic nephropathy
Hu et al have examined oxidative stress and inflammation in kidney in rats that fed on high fructose, the results showed inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6); oxidative stress index NOX2 and p22phox were upregulated in kidney, which could be partly restored by farnesoid X receptor (FXR) agonist chenodeoxycholic acid (CDCA) treatment [56]
Summary
Chronic kidney disease (CKD) is a major public health problem worldwide. Proteinuria is a common clinical signature and a potent predictor for the progression of CKD. Podocytes are highly differentiated glomerular epithelial cells which lie in the outmost layer of the glomerular filtration barrier. Podocyte foot processes interdigitate with the counterparts of neighboring cells to form the slit diaphragm, which constitutes the final barrier to prevent protein loss from vascular to urinary space. Podocyte injury has been considered as the most important early event initiating glomerulosclerosis in many proteinuric kidney diseases [1]. The slit diaphragm proteins, such as nephrin, podocin, CD2-associated protein (CD2AP), and canonical transient receptor potential channel (TRPC6), have been proved to play key role in maintaining normal podocyte structure and function [2]. Podocyte injury is generally presented as slit diaphragm disruption, actin cytoskeleton rearrangement, podocyte foot processes effacement, and proteinuria
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