摘要
包括 lysyl oxidase (哈鱼) ，涉及骨胶原生合成的酶为自发的肺的纤维变性作为潜在的治疗学的目标被建议了。哈鱼表示是显著地，在 bleomycin (BLM ) 的 upregulated 导致了肺纤维变性，并且哈鱼表示或哈鱼活动的抑制击倒减轻肺纤维变性。出人意料地，有在煽动性的阶段的哈鱼禁止者的鼠标的治疗，然而并非 fibrogenic 阶段，高效地减少骨胶原免职并且使肺建筑学正常化。哈鱼的抑制损害煽动性的房间渗入，发信号的 TGF- ，和 myofibroblast 累积。而且，哈鱼的宫外的表示敏化纤维变性抵抗的 Balb/c 老鼠到导致 BLM 的发炎和肺纤维变性。这些结果建议那条哈鱼为由在肺损害以后加重煽动性的反应和随后的纤维变性过程的导致 BLM 的试验性的肺纤维变性的前进是不可缺少的。
Enzymes involved in collagen biosynthesis, including lysyl oxidase （LOX）, have been proposed as potential therapeutic targets for idio- pathic 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 ceU infiltration, TGF-β signaling, and myofibroblast accumulation. Furthermore, ectopic expres- sion 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 subse- quent fibrosis process after lung injury.
基金
This work was supported by the National Basic Research Program of China （2010CB912102 and 2010CB529703） and the National Natural Science Foundation of China （31190061, 31371408, and 81430067）. G.G. is a scholar of the SA-SIBS Scholarship Program.
