A team of researchers at Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences, CAS, reported Oct 26 online in Journal of Molecular Cell Biology, identified Lysyl Oxidase (LOX) as a preventive target for lung fibrosis.
CHENG Tao and LIU Qingbo and their colleagues, supervised by Dr. GE Gaoxiang from SIBCB, discovered aberrant LOX expression and activity are essential to lung fibrosis, a progressive chronic interstitial lung disease with poor outcome.
Lung fibrosis is characterized by replacement of normal tissue with scar tissue, destruction of tissue architecture, and organ malfunction. Aberrant expression and activity of Lysyl Oxidase (LOX), the key enzyme mediating collagen crosslinking and deposition, have been believed to contribute to the pathological progression of pulmonary fibrosis. LOX is also proposed as potential therapeutic target for pulmonary fibrosis. Such scenario, however, lacks direct experimental data support.
Taking advantage of genetic mouse models and LOX pharmacological inhibitor, the researchers comprehensively investigated the functions of LOX at different stages in lung fibrosis progression. Unexpectedly, the researchers discovered that the function of LOX in lung fibrosis is more crucial at the early inflammatory stage, rather than at the late fibrogenic stage. LOX aggravates the inflammatory response and promotes lung fibrosis after lung injury. Inhibition of LOX impairs inflammatory cell infiltration, TGF-β signaling and myofibroblast accumulation. Interventions at the fibrogenic stage can not promisingly attenuate further progression of the disease. Fibrogenic stage is when most treatment applies in clinical practice. LOX, therefore, may serve as a preventive target, rather than a therapeutic target, for pulmonary fibrosis.
This work, entitled “Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation” was supported by grants from the National Natural Science Foundation of China and the Ministry of Science and Technology of China.
Fig. LOX aggravates the inflammatory response and promotes lung fibrosis after lung injury. (Image provided by GE Gaoxiang`s group)
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