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.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Uezumi A,Ito T,Morikawa D,Shimizu N,Yoneda T,Segawa M,Yamaguchi M,Ogawa R,Matev MM,Miyagoe-Suzuki Y,Takeda S,Tsujikawa K,Tsuchida K,Yamamoto H,Fukada Sdoi
10.1242/jcs.086629subject
Has Abstractpub_date
2011-11-01 00:00:00pages
3654-64issue
Pt 21eissn
0021-9533issn
1477-9137pii
jcs.086629journal_volume
124pub_type
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