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Uezumi, A; Fukada, S; Yamamoto, N; Ikemoto-uezumi, M; Nakatani, M; Morita, M; Yamaguchi, A; Yamada, H; Nishino, I; Hamada, Y; Tsuchida, K
Cell death & disease, 04/2014, Volume: 5Journal Article
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.
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