Cited by 680Muscle Physiology and DisordersNeurogenetic and Muscular Disorders ResearchCardiac Fibrosis and Remodeling

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 +7 more·2011·Journal of Cell Science

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.

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Crossref · 10.1242/jcs.086629

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  • In muscle disuse or pathological conditions, such as Duchenne muscular dystrophy, FAPs proliferate and differentiate into adipose and fibrous tissue.

    “In muscle disuse or pathological conditions, such as Duchenne muscular dystrophy, FAPs proliferate and differentiate into adipose and fibrous tissue.[ 41 ]”

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Authors
Uezumi, A., Ito, T., Morikawa, D., Shimizu, N., Yoneda, T., Segawa, M., Yamaguchi, M., Ogawa, R., Matev, M. M., Miyagoe-Suzuki, Y., Takeda, S., Tsujikawa, K., Tsuchida, K., Yamamoto, H., & Fukada, S.-I.
Affiliations
  • Fujita Health University (JP)
  • The University of Osaka (JP)
  • Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan
  • National Center of Neurology and Psychiatry (JP)
Corresponding author
Fukada, So-ichiro
Venue
Journal of Cell Science
Published
2011-11-01
Volume
124
Issue
21
Pages
3654-3664
ISSN
  • 0021-9533 (ISSN-L)
  • 1477-9137
OpenAlex
W1964124818
Cited by
680
References
38
Citations by year
2026: 47 · 2025: 54 · 2024: 57 · 2023: 52 · 2022: 58 · 2021: 61 · 2020: 69 · 2019: 55 · 2018: 46 · 2017: 36 · 2016: 42 · 2015: 34 · 2014: 28 · 2013: 28 · 2012: 13
FWCI
8.97
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Cell Science (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
Japan Society for the Promotion of Science (21590320, 21300149, 21790884)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Keywords
muscle fibrosis, adipogenesis, mesenchymal progenitor cells, PDGFRA, Duchenne muscular dystrophy, mdx mice, diaphragm, TGF-beta, type I collagen, fat deposition, cell of origin, clonal analysis, transplantation
MeSH terms
Animals, Cell Differentiation, Disease Models, Animal, Fibrosis, Humans, Mice, Inbred C57BL, Muscular Dystrophies, Adipocytes, Mice, Inbred mdx, Muscle, Skeletal, Receptor, Platelet-Derived Growth Factor alpha, Adipogenesis, Mice, Mesenchymal Stem Cells

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