Inhibition of platelet-derived growth factor signaling prevents muscle fiber growth during skeletal muscle hypertrophy

FEBS Lett. 2017 Mar;591(5):801-809. doi: 10.1002/1873-3468.12571. Epub 2017 Feb 17.

Abstract

The platelet-derived growth factor receptors alpha and beta (PDGFRα and PDGFRβ) mark fibroadipogenic progenitor cells/fibroblasts and pericytes in skeletal muscle, respectively. While the role that these cells play in muscle growth and development has been evaluated, it was not known whether the PDGF receptors activate signaling pathways that control transcriptional and functional changes during skeletal muscle hypertrophy. To evaluate this, we inhibited PDGFR signaling in mice subjected to a synergist ablation muscle growth procedure, and performed analyses 3 and 10 days after induction of hypertrophy. The results from this study indicate that PDGF signaling is required for fiber hypertrophy, extracellular matrix production, and angiogenesis that occur during muscle growth.

Keywords: extracellular matrix; platelet-derived growth factor; skeletal muscle.

Publication types

  • Letter
  • Research Support, N.I.H., Extramural

MeSH terms

  • Achilles Tendon / surgery
  • Animals
  • Animals, Newborn
  • Benzimidazoles / pharmacology
  • Extracellular Matrix / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Hypertrophy / genetics
  • Hypertrophy / metabolism*
  • Hypertrophy / physiopathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / physiopathology
  • Neovascularization, Physiologic*
  • Platelet-Derived Growth Factor / genetics
  • Platelet-Derived Growth Factor / metabolism
  • Quinolines / pharmacology
  • Receptor, Platelet-Derived Growth Factor alpha / antagonists & inhibitors
  • Receptor, Platelet-Derived Growth Factor alpha / genetics
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism*
  • Receptor, Platelet-Derived Growth Factor beta / antagonists & inhibitors
  • Receptor, Platelet-Derived Growth Factor beta / genetics
  • Receptor, Platelet-Derived Growth Factor beta / metabolism*
  • Signal Transduction
  • Weight-Bearing

Substances

  • Benzimidazoles
  • CP-673,451
  • Platelet-Derived Growth Factor
  • Quinolines
  • Receptor, Platelet-Derived Growth Factor alpha
  • Receptor, Platelet-Derived Growth Factor beta