Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655, Japan.
Curr Opin Pharmacol. 2010 Apr;10(2):156-65. doi: 10.1016/j.coph.2009.11.006. Epub 2010 Jan 4.
Dysfunction of endoplasmic reticulum (ER) maintaining protein homeostasis can result from various disturbances, including hypoxia or oxidative stress, which lead to an imbalance between protein-folding capacity and protein-folding load. This in turn leads to ER stress and induction of the unfolded protein response (UPR). The UPR initially serves as an adaptive response, but also induces apoptosis in cells under severe or prolonged ER stress. Accumulating evidence indicates that ER stress contributes to glomerular and tubular damages in kidney disease. These findings emphasize the importance of ER stress as a new progression factor and the interesting future possibility of renoprotective strategies targeting ER stress. These therapeutic approaches may act by breaking the vicious cycle of oxidative stress, hypoxia, and ER stress.
内质网（ER）功能障碍维持蛋白质稳态可能源于各种干扰，包括缺氧或氧化应激，这会导致蛋白质折叠能力和蛋白质折叠负荷之间的失衡。这反过来又导致内质网应激和未折叠蛋白反应（UPR）的诱导。UPR 最初作为一种适应性反应，但在严重或长期内质网应激下也会诱导细胞凋亡。越来越多的证据表明内质网应激导致肾脏疾病中的肾小球和肾小管损伤。这些发现强调了内质网应激作为一个新的进展因素的重要性，以及针对内质网应激的肾脏保护策略的有趣的未来可能性。这些治疗方法可能通过打破氧化应激、缺氧和内质网应激的恶性循环来发挥作用。
