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Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation Free
Tao Cheng1,†, Qingbo Liu1,†, Rui Zhang1, Ying Zhang1, Jianfeng Chen1, Ronghuan Yu2,3, and Gaoxiang Ge1,3,*
1State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
2Department of Respiratory Medicine, Shanghai Xu-Hui Central Hospital, Shanghai 200031, China
3Cancer Research Center, Shanghai Xu-Hui Central Hospital, Shanghai Clinical Center, Chinese Academy of Sciences, Shanghai 200031, China *Correspondence to:Gaoxiang Ge, E-mail:
J Mol Cell Biol, Volume 6, Issue 6, December 2014, 506-515,
Keyword: lysyl oxidase, lung fibrosis, inflammation, bleomycin, animal models, extracellular matrix

Enzymes involved in collagen biosynthesis, including lysyl oxidase (LOX), have been proposed as potential therapeutic targets for idiopathic 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 cell infiltration, TGF-β signaling, and myofibroblast accumulation. Furthermore, ectopic expression 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 subsequent fibrosis process after lung injury.