Arthritis Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Curr Opin Rheumatol. 2012 Nov;24(6):663-8. doi: 10.1097/BOR.0b013e3283588dbb.
To review the present knowledge of the role of endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in the pathogenesis of fibrotic diseases.
ER stress and UPR occur in a number of diseases associated with organ fibrosis; however, the contribution of these pathways to the fibrotic process has not been systematically investigated. Current studies suggest that prolonged ER stress may lead to fibrosis through activation of CCAAT/enhancer-binding homologous protein-mediated apoptosis, followed by an inflammatory response and release of profibrotic cytokines. A direct profibrotic role of UPR mediators in activation of TGF-β signaling has been shown in lung fibroblasts. In addition, activation of ER stress and UPR pathways in immune cells contributes to increased production of proinflammatory cytokines.
Although limited in scope, current studies strongly suggest that ER stress and UPR may play an important role during development of fibrosis. Further studies are warranted to gain additional insights into the relationship between these processes.
探讨内质网（ER）应激和未折叠蛋白反应（UPR）在纤维性疾病发病机制中的作用。
许多与器官纤维化相关的疾病中均存在 ER 应激和 UPR，但这些途径对纤维化过程的贡献尚未得到系统研究。目前的研究表明，持续的 ER 应激可能通过 CCAAT/增强子结合同源蛋白（CHOP）介导的细胞凋亡，继而引发炎症反应和促纤维化细胞因子的释放，从而导致纤维化。UPR 介质在肺成纤维细胞中 TGF-β 信号的激活中具有直接的促纤维化作用。此外，免疫细胞中 ER 应激和 UPR 途径的激活有助于增加促炎细胞因子的产生。
尽管目前的研究范围有限，但它们强烈表明 ER 应激和 UPR 可能在纤维化的发展过程中发挥重要作用。需要进一步的研究来深入了解这些过程之间的关系。
