Regulation of endoplasmic reticulum stress in models of kidney disease

Endoplasmic reticulum (ER) stress is induced by intrinsic and extrinsic factors and, in consequence, activates the unfolded protein response (UPR); which in an acute phase restores cellular homeostasis, whereas in a chronic phase promotes apoptosis. ER stress has been detected in a broad range of kidney diseases and the different degrees of ER stress and UPR stimulation could activate antioxidant and immune responses, autophagy, cell maintenance, inflammation, apoptosis and fibrosis. Understanding the regulation of ER stress and the UPR signaling pathways will allow to develop treatments that favor cellular functions in order to reduce the progression of diseases. The regulation of ER stress is carried out with natural or pharmacological compounds. The pharmacological inhibitors of ER stress commonly used are 4-phenylbutyric acid (4-PBA), tauroursodeoxycholic acid (TUDCA) and salubrinal, whereas pharmacological inducers of ER stress generally used are thapsigargin and tunicamycin. In addition, natural compounds such as polyphenols are able to induce and inhibit ER stress, and their effects are dose-dependent. In this review, we summarize notable findings on strategies of the induction of ER stress, as well as its inhibition, in the context of kidney diseases. Furthermore, these two methods of regulating ER stress are discussed.