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.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

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 S

doi

10.1242/jcs.086629

subject

Has Abstract

pub_date

2011-11-01 00:00:00

pages

3654-64

issue

Pt 21

eissn

0021-9533

issn

1477-9137

pii

jcs.086629

journal_volume

124

pub_type

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