Abstract
The endoplasmic reticulum (ER) plays an important role in the maintenance of protein homeostasis through its control of the concentration, conformation, folding, and trafficking of client proteins. Disturbances such as hypoxia, glucose depletion, and oxidative stress may lead to ER dysfunction, which can induce ER stress and the subsequent unfolded protein response (UPR). The UPR initially serves as an adaptive response, but will also induce apoptosis in cells under severe or prolonged ER stress. Oxidative stress and inflammation are compounded by ER stress via the UPR, suggesting the potential pathophysiological significance of this response across a wide range of diseases. Accumulating evidence indicates that ER stress contributes to glomerular and tubular damage in patients with acute and chronic kidney disease. In glomeruli, podocyte or mesangial dysfunction tends to induce the adaptive UPR, which involves ER chaperone expression and the attenuation of protein translation, to maintain ER homeostasis and ensure cell survival. In tubules, apoptosis resulting from epithelial cell damage is caused, at least in part, by the proapoptotic UPR. These findings emphasize the possibility of the development of novel renoprotective drugs which target ER stress.
Journal Section:
Minireview
Keywords:
Chronic kidney disease,
Acute kidney injury,
GRP78,
IRE1,
PERK,
ATF6,
Oxidative stress,
Inflammation
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