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Cell Death Dis. 2014 Apr 17;5:e1186. doi: 10.1038/cddis.2014.161.

Identification and characterization of PDGFRα+ mesenchymal progenitors in human skeletal muscle.

Author information

1
Division for Therapies against Intractable Diseases, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, Japan.
2
Department of Immunology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
3
Laboratory of Molecular Biology and Histochemistry, Fujita Health University, Aichi, Japan.
4
Department of Regenerative Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 35 Gengo, Morioka, Obu, Aichi 474-8511, Japan.
5
Department of Orthopaedic Surgery, Fujita Health University, Aichi, Japan.
6
Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan.
7
Department of Orthopedics, Tokushima Prefectural Central Hospital, 1-10-3 Kuramoto, Tokushima 770-8539, Japan.

Abstract

Fatty and fibrous connective tissue formation is a hallmark of diseased skeletal muscle and deteriorates muscle function. We previously identified non-myogenic mesenchymal progenitors that contribute to adipogenesis and fibrogenesis in mouse skeletal muscle. In this study, we report the identification and characterization of a human counterpart to these progenitors. By using PDGFRα as a specific marker, mesenchymal progenitors can be identified in the interstitium and isolated from human skeletal muscle. PDGFRα(+) cells represent a cell population distinct from CD56(+) myogenic cells, and adipogenic and fibrogenic potentials were highly enriched in the PDGFRα(+) population. Activation of PDGFRα stimulates proliferation of PDGFRα(+) cells through PI3K-Akt and MEK2-MAPK signaling pathways, and aberrant accumulation of PDGFRα(+) cells was conspicuous in muscles of patients with both genetic and non-genetic muscle diseases. Our results revealed the pathological relevance of PDGFRα(+) mesenchymal progenitors to human muscle diseases and provide a basis for developing therapeutic strategy to treat muscle diseases.

PMID:
24743741
PMCID:
PMC4001314
DOI:
10.1038/cddis.2014.161
[Indexed for MEDLINE]
Free PMC Article

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