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Full-Text Articles in Medicine and Health Sciences
Abrogation Of Transforming Growth Factor-Β-Induced Tissue Fibrosis In Tbricacol1a2cre Transgenic Mice By The Second Generation Tyrosine Kinase Inhibitor Ski-606 (Bosutinib)., Peter J. Wermuth, Sergio A. Jimenez
Abrogation Of Transforming Growth Factor-Β-Induced Tissue Fibrosis In Tbricacol1a2cre Transgenic Mice By The Second Generation Tyrosine Kinase Inhibitor Ski-606 (Bosutinib)., Peter J. Wermuth, Sergio A. Jimenez
Jefferson Institute of Molecular Medicine Papers and Presentations
Transforming growth factor-β (TGF-β) plays a crucial role in the pathogenesis of Systemic Sclerosis (SSc) and other fibrotic disorders. TGF-β-mediated c-Abl and Src kinase activation induces strong profibrotic cascade signaling. The purpose of this study was to test in vivo the antifibrotic activity of Bosutinib (SKI-606), a second generation c-Abl and Src kinase inhibitor, on TGF-β induced cutaneous and pulmonary fibrosis. For this purpose, we employed the TBRIcaCol1a2Cre transgenic mice expressing an inducible constitutively active TGF-β receptor 1 constitutively activated by Col1a promoter-mediated Cre recombinase. The mice were treated parenterally with 2.5, 5.0 or 10.0 mg/kg/day of Bosutinib for 42 …