King's College of London, Faculty of Life Sciences & Medicine, School of Cardiovascular Medicine & Sciences, Section Vascular Biology and Inflammation, British Heart Foundation Centre for Research Excellence, London, UK.
J Cell Mol Med. 2020 Nov;24(22):12910-12919. doi: 10.1111/jcmm.15999. Epub 2020 Oct 16.
Acute kidney injury (AKI) and chronic kidney disease (CKD) represent an important challenge for healthcare providers. The identification of new biomarkers/pharmacological targets for kidney disease is required for the development of more effective therapies. Several studies have shown the importance of the endoplasmic reticulum (ER) stress in the pathophysiology of AKI and CKD. ER is a cellular organelle devolved to protein biosynthesis and maturation, and cellular detoxification processes which are activated in response to an insult. This review aimed to dissect the cellular response to ER stress which manifests with activation of the unfolded protein response (UPR) with its major branches, namely PERK, IRE1α, ATF6 and the interplay between ER and mitochondria in the pathophysiology of kidney disease. Further, we will discuss the relationship between mediators of renal injury (with specific focus on vascular growth factors) and ER stress and UPR in the pathophysiology of both AKI and CKD with the aim to propose potential new targets for treatment for kidney disease.
急性肾损伤 (AKI) 和慢性肾脏病 (CKD) 是医疗保健提供者面临的重大挑战。需要寻找新的肾脏疾病生物标志物/药物靶点，以开发更有效的治疗方法。多项研究表明内质网 (ER) 应激在 AKI 和 CKD 的病理生理学中起着重要作用。ER 是一个负责蛋白质生物合成和成熟以及细胞解毒过程的细胞细胞器，在受到损伤时会被激活。本综述旨在剖析细胞对 ER 应激的反应，这种反应表现为未折叠蛋白反应 (UPR) 的激活及其主要分支，即 PERK、IRE1α、ATF6，以及 ER 和线粒体在肾脏病病理生理学中的相互作用。此外，我们还将讨论肾脏损伤介质（特别关注血管生长因子）与 ER 应激和 UPR 在 AKI 和 CKD 病理生理学中的关系，目的是为肾脏疾病的治疗提出潜在的新靶点。
