Endoplasmic reticulum stress and unfolded protein response in renal pathophysiology: Janus faces

Abstract

A number of pathophysiological insults lead to accumulation of unfolded proteins in the endoplasmic reticulum (ER) and cause ER stress. In response to accumulation of unfolded/misfolded proteins, cells adapt themselves to the stress condition via the unfolded protein response (UPR). For the cells, UPR is a double-edged sword. It triggers both prosurvival and proapoptotic signals. ER stress and UPR may, therefore, be involved in a diverse range of pathological situations. However, currently, information is limited regarding roles of ER stress and UPR in the renal pathophysiology. This review describes current knowledge on the relationship between ER stress and diseases and summarizes evidence for the link between ER stress/UPR and renal diseases.

Role of endoplasmic reticulum stress in drug‐induced toxicity

“…Cisplatin treatment can induce several types of adverse effects including GI disorders, kidney injury, neurotoxicity, hepatotoxicity, and cardiotoxicity (Kitamura 2008; Pabla and Dong 2008; Florea and Büsselberg 2011). Many investigations have been performed to decipher the mechanisms of cisplatin‐induced acute kidney injury because this frequent adverse effect limits the use of cisplatin in cancer therapy (Kitamura 2008; Pabla and Dong 2008).…”

“…Many investigations have been performed to decipher the mechanisms of cisplatin‐induced acute kidney injury because this frequent adverse effect limits the use of cisplatin in cancer therapy (Kitamura 2008; Pabla and Dong 2008). The emerging picture to explain cisplatin‐induced tubular cell injury and death is a combination of different pathophysiological events including mitochondrial dysfunction, ROS overproduction, increased tumor necrosis factor‐ α (TNF α ) generation, and ER stress (Kruidering et al.…”

“…The emerging picture to explain cisplatin‐induced tubular cell injury and death is a combination of different pathophysiological events including mitochondrial dysfunction, ROS overproduction, increased tumor necrosis factor‐ α (TNF α ) generation, and ER stress (Kruidering et al. 1997; Kitamura 2008; Pabla and Dong 2008; Servais et al. 2008; Mukhopadhyay et al.…”

Endoplasmic reticulum stress as a novel target to ameliorate epithelial-to-mesenchymal transition and apoptosis of human peritoneal mesothelial cells

“…20 The role of the UPR and ER stress has been demonstrated in idiopathic pulmonary fibrosis, as well as glomerulonephritis, diabetic nephropathy and drug-induced renal damage. 17,19,43,44 Despite ample evidence regarding the role of ER stress in organ fibrosis, the about ER stress and peritoneal fibrosis remain very limited. Previous studies revealed ultrastructural alterations of rough ER in the parietal peritoneum of patients on PD.…”

Arctigenin alleviates ER stress via activating AMPK

“…Second, ATG inhibited BFA-and tunicamycin-induced UPR, ie, the splicing of XBP-1 pre-mRNA, the phosphorylation of eIF2α and the expression of downstream UPR target genes, including Grp94, EDEM, ATF4, and CHOP. The UPR is involved in both survival and the apoptotic response [35] . Whether a cell survives or dies upon ER stress will depend on the balance of these opposing signals.…”