title: Identification and characterization of PDGFRα+ mesenchymal progenitors in human skeletal muscle.
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.
authors.affiliation: Division for Therapies against Intractable Diseases, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Uezumi
authors.affiliation: Department of Immunology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Fukada
authors.affiliation: Laboratory of Molecular Biology and Histochemistry, Fujita Health University, Aichi, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Department of Regenerative Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 35 Gengo, Morioka, Obu, Aichi 474-8511, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ikemoto-Uezumi
authors.affiliation: Division for Therapies against Intractable Diseases, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nakatani
authors.affiliation: Department of Orthopaedic Surgery, Fujita Health University, Aichi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Morita
authors.affiliation: Department of Orthopaedic Surgery, Fujita Health University, Aichi, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Yamaguchi
authors.affiliation: Department of Orthopaedic Surgery, Fujita Health University, Aichi, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Nishino
authors.affiliation: Department of Orthopedics, Tokushima Prefectural Central Hospital, 1-10-3 Kuramoto, Tokushima 770-8539, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hamada
authors.affiliation: Division for Therapies against Intractable Diseases, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tsuchida
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects; D050156:Adipogenesis / Q000187:drug effects; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D002469:Cell Separation / Q000379:methods*; D005434:Flow Cytometry; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D024510:Muscle Development / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D019002:CD56 Antigen; D016212:Transforming Growth Factor beta; D020796:Receptor, Platelet-Derived Growth Factor alpha
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