Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation

作     者：Tao Cheng Qingbo Liu Rui Zhang Ying Zhang Jianfeng Chen Ronghuan Yu Gaoxiang Ge 

作者机构：State Key Laboratory of Cell Biology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of SciencesShanghai 200031 China Department of Respiratory Medicine Shanghai Xu-Hui Central Hospital Shanghai 200031 China Cancer Research Center Shanghai Xu-Hui Central Hospital Shanghai Clinical Center Chinese Academy of Sciences Shanghai 200031 China 

出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)

年 卷 期：2014年第8卷第6期

页      面：506-515页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 07[理学] 071002[理学-动物学] 10[医学] 

基　　金：This work was supported by the National Basic Research Program of China (2010CB912102 and 2010CB529703) and the National Natural Science Foundation of China (31190061  31371408  and 81430067). G.G. is a scholar of the SA-SIBS Scholarship Program 

主　　题：lysyl oxidase lung fibrosis inflammation bleomycin animal models extracellular matrix 

摘      要：Enzymes involved in collagen biosynthesis, including lysyl oxidase （LOX）, have been proposed as potential therapeutic targets for idio- pathic pulmonary fibrosis. LOX expression is significantly upregulated in bleomycin （BLM）-induced lung fibrosis, and knockdown of LOX expression or inhibition of LOX activity alleviates the lung fibrosis. Unexpectedly, treatment of the mice with LOX inhibitor at the inflammatory stage, but not the fibrogenic stage, efficiently reduces collagen deposition and normalizes lung architecture. Inhibition of LOX impairs inflammatory ceU infiltration, TGF-β signaling, and myofibroblast accumulation. Furthermore, ectopic expres- sion of LOX sensitizes the fibrosis-resistant Balb/c mice to BLM-induced inflammation and lung fibrosis. These results suggest that LOX is indispensable for the progression of BLM-induced experimental lung fibrosis by aggravating the inflammatory response and subse- quent fibrosis process after lung injury.