title: Targeting of Discoidin Domain Receptor 2 (DDR2) Prevents Myofibroblast Activation and Neovessel Formation During Pulmonary Fibrosis.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Hu
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Huan
authors.initials: H
authors.lastname: Bian
authors.affiliation: Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Bu
authors.affiliation: 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.
authors.forename: Shuya
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Pan
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Jiangtian
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Lai
authors.affiliation: Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Di
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Human Anatomy, Histology, and Embryology, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Chuchao
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Libo
authors.initials: L
authors.lastname: Yao
authors.affiliation: Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Su
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D000070820:Discoidin Domain Receptor 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D051379:Mice; D058628:Myofibroblasts / Q000166:cytology* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D011658:Pulmonary Fibrosis / Q000188:drug therapy / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C000603239:DDR2 protein, human; D000070820:Discoidin Domain Receptor 2