title: Imatinib attenuates severe mouse dystrophy and inhibits proliferation and fibrosis-marker expression in muscle mesenchymal progenitors.
abstract: Imatinib mesylate inhibits signaling of tyrosine kinase receptors, including PDGFRα, and has been used for human cancer therapy. Recent studies have indicated that imatinib is also effective in treatment of some chronic diseases with fibrosis. Fibrosis is the feature of Duchenne muscular dystrophy. It has been reported that imatinib attenuates fibrosis in mdx mice. Recently we revealed that PDGFRα is specifically expressed in muscle mesenchymal progenitors, which are the origin of muscle fibrosis. Here, we show that imatinib ameliorates the muscular pathology of DBA/2-mdx, a more severe mouse muscular dystrophy. In addition, imatinib inhibits both the proliferation and fibrosis marker expression induced by PDGF-AA in muscle mesenchymal progenitors in vitro. Importantly, the effective dose of imatinib on muscle mesenchymal progenitors did not inhibit myoblast proliferation. These results suggest that imatinib targets mesenchymal progenitors, and that a therapeutic strategy targeting mesenchymal progenitors could be a potential treatment for muscular dystrophies.
authors: Laboratory of Cell Biology and Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors: Takahito
authors: T
authors: Ito
authors: Ryo
authors: R
authors: Ogawa
authors: Akiyoshi
authors: A
authors: Uezumi
authors: Takuji
authors: T
authors: Ohtani
authors: Yoko
authors: Y
authors: Watanabe
authors: Kazutake
authors: K
authors: Tsujikawa
authors: Yuko
authors: Y
authors: Miyagoe-Suzuki
authors: Shin'ichi
authors: S
authors: Takeda
authors: Hiroshi
authors: H
authors: Yamamoto
authors: So-ichiro
authors: S
authors: Fukada
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D000068877:Imatinib Mesylate; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D051379:Mice; D008811:Mice, Inbred DBA; D018101:Mice, Inbred mdx; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010879:Piperazines / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000494:pharmacology*; D032496:Satellite Cells, Skeletal Muscle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001549:Benzamides; D010879:Piperazines; D010982:Platelet-Derived Growth Factor; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; C075278:platelet-derived growth factor A; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases