Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation

T Cheng, Q Liu, R Zhang, Y Zhang… - Journal of molecular …, 2014 - academic.oup.com
T Cheng, Q Liu, R Zhang, Y Zhang, J Chen, R Yu, G Ge
Journal of molecular cell biology, 2014academic.oup.com
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 …
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.
Oxford University Press