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

Cell Death Dis. 2014 Apr 17;5(4):e1186. doi: 10.1038/cddis.2014.161.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / drug effects
  • Adipogenesis / drug effects
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Biomarkers / metabolism
  • CD56 Antigen / metabolism
  • Cell Separation / methods*
  • Flow Cytometry
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Middle Aged
  • Muscle Development / drug effects
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism
  • Muscle, Skeletal / cytology*
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism*
  • Signal Transduction / drug effects
  • Transforming Growth Factor beta / pharmacology

Substances

  • Biomarkers
  • CD56 Antigen
  • Transforming Growth Factor beta
  • Receptor, Platelet-Derived Growth Factor alpha