Antifibrotic Effects of Focal Adhesion Kinase Inhibitor in Bleomycin-Induced Pulmonary Fibrosis in Mice

• DOI: 10.1165/rcmb.2012-0277oc
• Publication Date: 2013-05-03T22:08:15Z
• Authors: Katsuhiro Kinoshita; Yoshinori Aono; Momoyo Azuma; Jun Kishi; Akio Takezaki; Masami Kishi; Hideki Makino; Hiroyasu Okazaki; Hisanori Uehara; Keisuke Izumi; Saburo Sone; Yasuhiko Nishioka
• Keywords: Platelet-Derived Growth Factor; 0301 basic medicine; Morpholines; Cell Differentiation; Epithelial Cells; Mesenchymal Stem Cells; DNA; Fibroblasts; Actins; Collagen Type I; 3. Good health; Mice, Inbred C57BL; Bleomycin; Mice; 03 medical and health sciences; Focal Adhesion Kinase 1; Animals; Female; Insulin-Like Growth Factor I; Phosphorylation; Myofibroblasts; Protein Kinase Inhibitors; Cell Proliferation

Focal adhesion kinase (FAK) is a nonreceptor tyrosine involved in various biological functions, including cell survival, proliferation, migration, and adhesion. FAK an essential factor for transforming growth β to induce myofibroblast differentiation. In the present study, we investigated whether targeted inhibition of by using specific inhibitor, TAE226, has potential regulate pulmonary fibrosis. TAE226 showed inhibitory activity autophosphorylation at 397 lung fibroblasts. The addition inhibited proliferation fibroblasts response factors, platelet-derived insulin-like I, vitro. strongly suppressed production type I collagen Furthermore, treatment with reduced expression α-smooth muscle actin induced β, indicating differentiation myofibroblasts. Administration ameliorated fibrosis bleomycin mice even when used late treatment. number proliferating mesenchymal cells was lungs TAE226-treated mice. These data suggest that signal plays significant role progression it can become promising target therapeutic approaches