Zhao Hu, Bian Huan, Bu Xin, Zhang Shuya, Zhang Pan, Yu Jiangtian, Lai Xiaofeng, Li Di, Zhu Chuchao, Yao Libo, Su Jin
Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi'an, People's Republic of China.
Department of Biochemistry and Molecular Biology, Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, People's Republic of China.
Mol Ther. 2016 Oct;24(10):1734-1744. doi: 10.1038/mt.2016.109. Epub 2016 May 27.
Idiopathic pulmonary fibrosis (IPF) is a lethal human disease with short survival time and few treatment options. Herein, we demonstrated that discoidin domain receptor 2 (DDR2), a receptor tyrosine kinase that predominantly transduces signals from fibrillar collagens, plays a critical role in the induction of fibrosis and angiogenesis in the lung. In vitro cell studies showed that DDR2 can synergize the actions of both transforming growth factor (TGF)-β and fibrillar collagen to stimulate lung fibroblasts to undergo myofibroblastic changes and vascular endothelial growth factor (VEGF) expression. In addition, we confirmed that late treatment of the injured mice with specific siRNA against DDR2 or its kinase inhibitor exhibited therapeutic efficacy against lung fibrosis. Thus, this study not only elucidated novel mechanisms by which DDR2 controls the development of pulmonary fibrosis, but also provided candidate target for the intervention of this stubborn disease.
特发性肺纤维化（IPF）是一种致命的人类疾病，生存时间短且治疗选择有限。在此，我们证明了盘状结构域受体2（DDR2），一种主要转导来自纤维状胶原蛋白信号的受体酪氨酸激酶，在肺部纤维化和血管生成的诱导中起关键作用。体外细胞研究表明，DDR2可协同转化生长因子（TGF）-β和纤维状胶原蛋白的作用，刺激肺成纤维细胞发生肌成纤维细胞变化并表达血管内皮生长因子（VEGF）。此外，我们证实，用针对DDR2的特异性siRNA或其激酶抑制剂对受伤小鼠进行晚期治疗，对肺纤维化具有治疗效果。因此，本研究不仅阐明了DDR2控制肺纤维化发展的新机制，还为干预这种顽固性疾病提供了候选靶点。
