Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation

被引:66
作者
Cheng, Tao [1 ]
Liu, Qingbo [1 ]
Zhang, Rui [1 ]
Zhang, Ying [1 ]
Chen, Jianfeng [1 ]
Yu, Ronghuan [2 ,3 ]
Ge, Gaoxiang [1 ,3 ]
机构
[1] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China
[2] Shanghai Xu Hui Cent Hosp, Dept Resp Med, Shanghai 200031, Peoples R China
[3] Chinese Acad Sci, Shanghai Clin Ctr, Shanghai Xu Hui Cent Hosp, Canc Res Ctr, Shanghai 200031, Peoples R China
基金
中国国家自然科学基金;
关键词
lysyl oxidase; lung fibrosis; inflammation; bleomycin; animal models; extracellular matrix; PULMONARY-FIBROSIS; COLLAGEN; CANCER; DISEASE; ROLES; METASTASIS; EXPRESSION; ENZYME;
D O I
10.1093/jmcb/mju039
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 LOXimpairs inflammatory cell infiltration, TGF-bsignaling, andmyofibroblast accumulation. Furthermore, ectopic expression of LOXsensitizes 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.
引用
收藏
页码:506 / 515
页数:10
相关论文
共 42 条
[1]   Fibrogenic Reactions in Lung Disease [J].
Araya, Jun ;
Nishimura, Stephen L. .
ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE, 2010, 5 :77-98
[2]   The Role of Lysyl Oxidase in SRC-Dependent Proliferation and Metastasis of Colorectal Cancer [J].
Baker, Ann-Marie ;
Cox, Thomas R. ;
Bird, Demelza ;
Lang, Georgina ;
Murray, Graeme I. ;
Sun, Xiao-Feng ;
Southall, Stacey M. ;
Wilson, Jon R. ;
Erler, Janine T. .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2011, 103 (05) :407-424
[3]   Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment [J].
Barry-Hamilton, Vivian ;
Spangler, Rhyannon ;
Marshall, Derek ;
McCauley, Scott ;
Rodriguez, Hector M. ;
Oyasu, Miho ;
Mikels, Amanda ;
Vaysberg, Maria ;
Ghermazien, Haben ;
Wai, Carol ;
Garcia, Carlos A. ;
Velayo, Arleene C. ;
Jorgensen, Brett ;
Biermann, Donna ;
Tsai, Daniel ;
Green, Jennifer ;
Zaffryar-Eilot, Shelly ;
Holzer, Alison ;
Ogg, Scott ;
Thai, Dung ;
Neufeld, Gera ;
Van Vlasselaer, Peter ;
Smith, Victoria .
NATURE MEDICINE, 2010, 16 (09) :1009-U107
[4]  
CHANOKI M, 1995, BRIT J DERMATOL, V133, P710
[5]  
COUNTS DF, 1981, J PHARMACOL EXP THER, V219, P675
[6]   LOX-Mediated Collagen Crosslinking Is Responsible for Fibrosis-Enhanced Metastasis (Publication with Expression of Concern. See vol. 79, pg. 5124, 2019) [J].
Cox, Thomas R. ;
Bird, Demelza ;
Baker, Ann-Marie ;
Barker, Holly E. ;
Ho, Melisa W-Y ;
Lang, Georgina ;
Erler, Janine T. .
CANCER RESEARCH, 2013, 73 (06) :1721-1732
[7]  
Decitre M, 1998, LAB INVEST, V78, P143
[8]   Strategies for treating idiopathic pulmonary fibrosis [J].
du Bois, R. M. .
NATURE REVIEWS DRUG DISCOVERY, 2010, 9 (02) :129-140
[9]   Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair [J].
Duffield, JS ;
Forbes, SJ ;
Constandinou, CM ;
Clay, S ;
Partolina, M ;
Vuthoori, S ;
Wu, SJ ;
Lang, R ;
Iredale, JP .
JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (01) :56-65
[10]   Hypoxia-Induced Lysyl Oxidase Is a Critical Mediator of Bone Marrow Cell Recruitment to Form the Premetastatic Niche [J].
Erler, Janine T. ;
Bennewith, Kevin L. ;
Cox, Thomas R. ;
Lang, Georgina ;
Bird, Demelza ;
Koong, Albert ;
Le, Quynh-Thu ;
Giaccia, Amato J. .
CANCER CELL, 2009, 15 (01) :35-44