Myogenic Progenitor Cells Control Extracellular Matrix Production by Fibroblasts during Skeletal Muscle Hypertrophy

Cell Stem Cell. 2017 Jan 5;20(1):56-69. doi: 10.1016/j.stem.2016.09.010. Epub 2016 Nov 10.

Abstract

Satellite cells, the predominant stem cell population in adult skeletal muscle, are activated in response to hypertrophic stimuli and give rise to myogenic progenitor cells (MPCs) within the extracellular matrix (ECM) that surrounds myofibers. This ECM is composed largely of collagens secreted by interstitial fibrogenic cells, which influence satellite cell activity and muscle repair during hypertrophy and aging. Here we show that MPCs interact with interstitial fibrogenic cells to ensure proper ECM deposition and optimal muscle remodeling in response to hypertrophic stimuli. MPC-dependent ECM remodeling during the first week of a growth stimulus is sufficient to ensure long-term myofiber hypertrophy. MPCs secrete exosomes containing miR-206, which represses Rrbp1, a master regulator of collagen biosynthesis, in fibrogenic cells to prevent excessive ECM deposition. These findings provide insights into how skeletal stem and progenitor cells interact with other cell types to actively regulate their extracellular environments for tissue maintenance and adaptation.

Keywords: Pax7; collagen; exosomes; extracellular matrix; fibrosis; hypertrophy; microRNA; muscle; muscle progenitor cells; satellite cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / metabolism
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Collagen / genetics
  • Collagen / metabolism
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Exosomes / drug effects
  • Exosomes / metabolism
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / genetics
  • Extracellular Matrix / metabolism*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Gene Deletion
  • Gene Knockdown Techniques
  • Hypertrophy
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Models, Biological
  • Muscle Development* / drug effects
  • Muscle Development* / genetics
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Skeletal / pathology
  • Muscle, Skeletal / pathology*
  • NIH 3T3 Cells
  • PAX7 Transcription Factor / metabolism
  • Ribonuclease III / metabolism
  • Satellite Cells, Skeletal Muscle / drug effects
  • Satellite Cells, Skeletal Muscle / metabolism
  • Stem Cells / drug effects
  • Stem Cells / metabolism*
  • Tamoxifen / pharmacology

Substances

  • Carrier Proteins
  • MicroRNAs
  • PAX7 Transcription Factor
  • Tamoxifen
  • Collagen
  • Ribonuclease III