title: Fibrosis and adipogenesis originate from a common mesenchymal progenitor in skeletal muscle.
abstract: Accumulation of adipocytes and collagen type-I-producing cells (fibrosis) is observed in muscular dystrophies. The origin of these cells had been largely unknown, but recently we identified mesenchymal progenitors positive for platelet-derived growth factor receptor alpha (PDGFRα) as the origin of adipocytes in skeletal muscle. However, the origin of muscle fibrosis remains largely unknown. In this study, clonal analyses show that PDGFRα(+) cells also differentiate into collagen type-I-producing cells. In fact, PDGFRα(+) cells accumulated in fibrotic areas of the diaphragm in the mdx mouse, a model of Duchenne muscular dystrophy. Furthermore, mRNA of fibrosis markers was expressed exclusively in the PDGFRα(+) cell fraction in the mdx diaphragm. Importantly, TGF-β isoforms, known as potent profibrotic cytokines, induced expression of markers of fibrosis in PDGFRα(+) cells but not in myogenic cells. Transplantation studies revealed that fibrogenic PDGFRα(+) cells mainly derived from pre-existing PDGFRα(+) cells and that the contribution of PDGFRα(-) cells and circulating cells was limited. These results indicate that mesenchymal progenitors are the main origin of not only fat accumulation but also fibrosis in skeletal muscle.
authors: Division for Therapies Against Intractable Diseases, Institute for Comprehensive Medical Science, Fujita Health University, Kutsukake-cho, Toyoake, Aichi 470-1192,  Japan.
authors: Akiyoshi
authors: A
authors: Uezumi
authors: Takahito
authors: T
authors: Ito
authors: Daisuke
authors: D
authors: Morikawa
authors: Natsuko
authors: N
authors: Shimizu
authors: Tomohiro
authors: T
authors: Yoneda
authors: Masashi
authors: M
authors: Segawa
authors: Masahiko
authors: M
authors: Yamaguchi
authors: Ryo
authors: R
authors: Ogawa
authors: Miroslav M
authors: MM
authors: Matev
authors: Yuko
authors: Y
authors: Miyagoe-Suzuki
authors: Shin'ichi
authors: S
authors: Takeda
authors: Kazutake
authors: K
authors: Tsujikawa
authors: Kunihiro
authors: K
authors: Tsuchida
authors: Hiroshi
authors: H
authors: Yamamoto
authors: So-ichiro
authors: S
authors: Fukada
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis; D000818:Animals; D002454:Cell Differentiation; D004195:Disease Models, Animal; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism; D009136:Muscular Dystrophies / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D020796:Receptor, Platelet-Derived Growth Factor alpha