Antifibrotic effects of focal adhesion kinase inhibitor in bleomycin-induced pulmonary fibrosis in mice
| Autor: | Katsuhiro Kinoshita, Hideki Makino, Hisanori Uehara, Momoyo Azuma, Yoshinori Aono, Saburo Sone, Yasuhiko Nishioka, Masami Kishi, Akio Takezaki, Hiroyasu Okazaki, Jun Kishi, Keisuke Izumi |
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| Rok vydání: | 2013 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_treatment Morpholines Pulmonary Fibrosis Clinical Biochemistry PTK2 Collagen Type I Focal adhesion Bleomycin Mice Transforming Growth Factor beta Pulmonary fibrosis medicine Animals Insulin-Like Growth Factor I Phosphorylation Myofibroblasts Molecular Biology Protein Kinase Inhibitors Cell Proliferation Platelet-Derived Growth Factor biology Chemistry Growth factor Cell Differentiation Epithelial Cells Mesenchymal Stem Cells Cell Biology DNA Fibroblasts medicine.disease Actins Cell biology Mice Inbred C57BL Focal Adhesion Kinase 1 biology.protein Cancer research Tyrosine Female Myofibroblast Tyrosine kinase Platelet-derived growth factor receptor Transforming growth factor |
| Zdroj: | American journal of respiratory cell and molecular biology. 49(4) |
| ISSN: | 1535-4989 |
| Popis: | Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase involved in various biological functions, including cell survival, proliferation, migration, and adhesion. FAK is an essential factor for transforming growth factor β to induce myofibroblast differentiation. In the present study, we investigated whether the targeted inhibition of FAK by using a specific inhibitor, TAE226, has the potential to regulate pulmonary fibrosis. TAE226 showed inhibitory activity of autophosphorylation of FAK at tyrosine 397 in lung fibroblasts. The addition of TAE226 inhibited the proliferation of lung fibroblasts in response to various growth factors, including platelet-derived growth factor and insulin-like growth factor I, in vitro. TAE226 strongly suppressed the production of type I collagen by lung fibroblasts. Furthermore, treatment of fibroblasts with TAE226 reduced the expression of α-smooth muscle actin induced by transforming growth factor β, indicating the inhibition of differentiation of fibroblasts to myofibroblasts. Administration of TAE226 ameliorated the pulmonary fibrosis induced by bleomycin in mice even when used late in the treatment. The number of proliferating mesenchymal cells was reduced in the lungs of TAE226-treated mice. These data suggest that FAK signal plays a significant role in the progression of pulmonary fibrosis and that it can become a promising target for therapeutic approaches to pulmonary fibrosis. |
| Databáze: | OpenAIRE |
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