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.
| Original language | English |
|---|---|
| Pages (from-to) | 3654-3664 |
| Number of pages | 11 |
| Journal | Journal of Cell Science |
| Volume | 124 |
| Issue number | 21 |
| DOIs | |
| Publication status | Published - 01-11-2011 |
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All Science Journal Classification (ASJC) codes
- Cell Biology
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Fibrosis and adipogenesis originate from a common mesenchymal progenitor in skeletal muscle. / Uezumi, Akiyoshi; Ito, Takahito; Morikawa, Daisuke; Shimizu, Natsuko; Yoneda, Tomohiro; Segawa, Masashi; Yamaguchi, Masahiko; Ogawa, Ryo; Matev, Miroslav M.; Miyagoe-Suzuki, Yuko; Takeda, Shin'ichi; Tsujikawa, Kazutake; Tsuchida, Kunihiro; Yamamoto, Hiroshi; Fukada, So Ichiro.
In: Journal of Cell Science, Vol. 124, No. 21, 01.11.2011, p. 3654-3664.Research output: Contribution to journal › Article
TY - JOUR
T1 - Fibrosis and adipogenesis originate from a common mesenchymal progenitor in skeletal muscle
AU - Uezumi, Akiyoshi
AU - Ito, Takahito
AU - Morikawa, Daisuke
AU - Shimizu, Natsuko
AU - Yoneda, Tomohiro
AU - Segawa, Masashi
AU - Yamaguchi, Masahiko
AU - Ogawa, Ryo
AU - Matev, Miroslav M.
AU - Miyagoe-Suzuki, Yuko
AU - Takeda, Shin'ichi
AU - Tsujikawa, Kazutake
AU - Tsuchida, Kunihiro
AU - Yamamoto, Hiroshi
AU - Fukada, So Ichiro
PY - 2011/11/1
Y1 - 2011/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=81355149472&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=81355149472&partnerID=8YFLogxK
U2 - 10.1242/jcs.086629
DO - 10.1242/jcs.086629
M3 - Article
C2 - 22045730
AN - SCOPUS:81355149472
VL - 124
SP - 3654
EP - 3664
JO - Journal of Cell Science
JF - Journal of Cell Science
SN - 0021-9533
IS - 21
ER -