Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation - PubMed (original) (raw)

doi: 10.1093/jmcb/mju039. Epub 2014 Oct 26.

Affiliations

• PMID: 25348956
• DOI: 10.1093/jmcb/mju039

Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation

Tao Cheng et al. J Mol Cell Biol. 2014 Dec.

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.

Keywords: animal models; bleomycin; extracellular matrix; inflammation; lung fibrosis; lysyl oxidase.

© The Author (2014). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

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