Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation
Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation
复制标题
赖氨酰氧化酶通过调节炎症促进博莱霉素诱导的肺纤维化
DOI：
10.1093/jmcb/mju039
复制
发表时间：
2014-12-01
影响因子：
5.5
通讯作者：
Ge, Gaoxiang
中科院分区：
文献类型：
--
作者：
Cheng, Tao;Liu, Qingbo;Ge, Gaoxiang
参与胶原生物合成的酶，包括赖氨酸氧化酶（LOX），被认为是特发性肺纤维化的潜在治疗靶点。在博来霉素（BLM）诱导的肺纤维化中，LOX表达显著上调，下调LOX表达或抑制LOX活性可减轻肺纤维化。出乎意料的是，在炎症期而不是纤维化期使用LOX抑制剂治疗小鼠，有效地减少胶原沉积并使肺结构正常化。抑制loxx可损害炎症细胞浸润、tgf -b信号传导和肌成纤维细胞积累。此外，lox异位表达使抗纤维化Balb/c小鼠对blm诱导的炎症和肺纤维化敏感。这些结果表明，通过加重肺损伤后的炎症反应和随后的纤维化过程，LOX在blm诱导的实验性肺纤维化的进展中是不可或缺的。
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.