title: Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation.
abstract: 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.
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Ronghuan
authors.initials: R
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China Cancer Research Center, Shanghai Xu-Hui Central Hospital, Shanghai Clinical Center, Chinese Academy of Sciences, Shanghai 200031, China gxge@sibcb.ac.cn.
authors.forename: Gaoxiang
authors.initials: G
authors.lastname: Ge
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects* / Q000494:pharmacology; D001761:Bleomycin / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008168:Lung / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008249:Protein-Lysine 6-Oxidase / Q000096:biosynthesis*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology
chemical_list: D000903:Antibiotics, Antineoplastic; D001761:Bleomycin; D008249:Protein-Lysine 6-Oxidase
keywords: animal models; bleomycin; extracellular matrix; inflammation; lung fibrosis; lysyl oxidase