吡非尼酮
未折叠蛋白反应
特发性肺纤维化
氧化应激
细胞凋亡
内质网
体内
医学
线粒体
药理学
癌症研究
肺纤维化
脂多糖
肺
内科学
纤维化
化学
免疫学
生物
生物化学
生物技术
作者
Yingzhen Du,Pingjun Zhu,Xi Wang,Mi Mu,Hongxia Li,Yanhong Gao,Xuebing Qin,Sheng Wang,Zhijian Zhang,Geping Qu,Guogang Xu,Christopher Chang,Tianzhi Li,Xiangqun Fang,YU Sen-yang
标识
DOI:10.1016/j.jaut.2020.102464
摘要
Pirfenidone has been widely used in the treatment of idiopathic pulmonary fibrosis (IPF). However, the role of pirfenidone in LPS-induced acute lung injury (ALI) remains unclear. This study aims to investigate the protective effects of pirfenidone in ALI and to explore its underlying mechanism. Pirfenidone clearly reduces LPS-triggered ALI as indicated by significant pathological alterations, reduced oxidative stress and inflammatory responses in vivo. Furthermore, pirfenidone also blocks apoptosis of LPS-induced alveolar epithelial type II (ATII) cells through inhibition of endoplasmic reticulum (ER) stress and mitochondrial injury in vivo and in vitro. A lower expression level of BAP31, an ER transmembrane protein, was found to be associated with ALI followed LPS challenge. The reintroduction of BAP31 blunted LPS induced ER stress and mitochondrial damage and therefore alleviated ATII cell apoptosis, which correlated with pirfenidone treatment. Knockdown of BAP31 expression in pirfenidone treated ATII cells re-activated ER stress, mitochondrial damage and followed cellular apoptosis. In summary, this study confirms the beneficial effect of pirfenidone on ER stress and mitochondrial dysfunction mediated apoptosis via upregulation of BAP31. Our results demonstrated that pirfenidone may be considered as a potential agent for the treatment of ALI in the future.
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