The role of endoplasmic reticulum stress and the unfolded protein response in fibrosis.
The role of endoplasmic reticulum stress and the unfolded protein response in fibrosis.
复制标题
DOI：
10.1097/bor.0b013e3283588dbb
复制
发表时间：
2012-11
影响因子：
5.1
通讯作者：
Trojanowska M
中科院分区：
文献类型：
--
作者：
Lenna S;Trojanowska M
综述内质网应激和未折叠蛋白反应在纤维化疾病发病机制中的作用。ER应激和UPR发生在许多与器官纤维化相关的疾病中;然而，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，长期的ER应激可能会导致纤维化通过激活CCAAT/增强子结合同源蛋白介导的细胞凋亡，随后的炎症反应和释放促纤维化细胞因子。在肺成纤维细胞中已经显示了UPR介质在TGF-β信号传导的活化中的直接促纤维化作用。此外，免疫细胞中ER应激和UPR途径的激活有助于促炎细胞因子的产生增加。虽然范围有限，但目前的研究强烈表明，ER应激和UPR可能在纤维化的发展过程中发挥重要作用。进一步的研究是必要的，以获得更多的见解，这些过程之间的关系。
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.