Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
IUBMB Life. 2020 Feb;72(2):187-197. doi: 10.1002/iub.2154. Epub 2019 Aug 24.
The endoplasmic reticulum (ER) receives unfolded proteins predestined for the secretory pathway or to be incorporated as transmembrane proteins. The ER has to accommodate the proper folding and glycosylation of these proteins and also to properly incorporate transmembrane proteins. However, under various circumstances, the proteins shuttling through the ER can be misfolded and undergo aggregation, which causes activation of the unfolded protein response (UPR). The UPR is mediated through three primary pathways: activating transcription factor-6, inositol-requiring enzyme-1 (IRE1), and PKR-like endoplasmic reticulum kinase, which up-regulate ER folding chaperones and temporarily suppress protein translation. The UPR can be both cytoprotective and/or cytotoxic depending on the duration of UPR activation and the type of host cell. Proteostasis controls stem cell function, while stress responses affect stem cell identity and differentiation. The present review aimed to explore and discuss the effects of the UPR pathways on mesenchymal stem cells.
内质网 (ER) 接收预定用于分泌途径的未折叠蛋白或要整合为跨膜蛋白的未折叠蛋白。ER 必须适应这些蛋白质的正确折叠和糖基化，并且还必须正确整合跨膜蛋白。然而，在各种情况下，穿过 ER 的蛋白质可能会错误折叠并发生聚集，从而导致未折叠蛋白反应 (UPR) 的激活。UPR 通过三种主要途径介导：激活转录因子 6、肌醇需求酶 1 (IRE1) 和 PKR 样内质网激酶，它们上调 ER 折叠伴侣并暂时抑制蛋白质翻译。UPR 的作用既可以是细胞保护的，也可以是细胞毒性的，具体取决于 UPR 激活的持续时间和宿主细胞的类型。蛋白质稳态控制干细胞功能，而应激反应影响干细胞的特性和分化。本综述旨在探讨和讨论 UPR 途径对间充质干细胞的影响。
