Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Int J Mol Sci. 2021 Feb 22;22(4):2161. doi: 10.3390/ijms22042161.
The endoplasmic reticulum (ER) is the central site for folding, post-translational modifications, and transport of secretory and membrane proteins. An imbalance between the load of misfolded proteins and the folding capacity of the ER causes ER stress and an unfolded protein response. Emerging evidence has shown that ER stress or the derangement of ER proteostasis contributes to the development and progression of a variety of glomerular and tubular diseases. This review gives a comprehensive summary of studies that have elucidated the role of the three ER stress signaling pathways, including inositol-requiring enzyme 1 (IRE1), protein kinase R-like ER kinase (PERK), and activating transcription factor 6 (ATF6) signaling in the pathogenesis of kidney disease. In addition, we highlight the recent discovery of ER-associated biomarkers, including MANF, ERdj3, ERdj4, CRELD2, PDIA3, and angiogenin. The implementation of these novel biomarkers may accelerate early diagnosis and therapeutic intervention in rare kidney disease.
内质网（ER）是折叠、翻译后修饰和分泌蛋白及膜蛋白运输的中心场所。错误折叠蛋白的负荷与 ER 的折叠能力之间的失衡会导致 ER 应激和未折叠蛋白反应。新出现的证据表明，ER 应激或 ER 蛋白稳态的紊乱有助于多种肾小球和肾小管疾病的发生和发展。这篇综述全面总结了阐明 ER 应激信号通路（包括肌醇需求酶 1（IRE1）、蛋白激酶 R 样内质网激酶（PERK）和激活转录因子 6（ATF6）信号通路）在肾脏疾病发病机制中的作用的研究。此外，我们还强调了 ER 相关生物标志物（包括 MANF、ERdj3、ERdj4、CRELD2、PDIA3 和血管生成素）的最新发现。这些新型生物标志物的实施可能会加速罕见肾脏疾病的早期诊断和治疗干预。
