Age-related decrease in muscle satellite cells is accompanied with diminished expression of early growth response 3 in mice

Mol Biol Rep. 2020 Feb;47(2):977-986. doi: 10.1007/s11033-019-05189-5. Epub 2019 Nov 16.

Abstract

Skeletal muscle regeneration is mostly dependent on muscle satellite cells. Proper muscle regeneration requires enough number of satellite cells. Recent studies have suggested that the number of satellite cells in skeletal muscle declines as we age, leading to the impairment of muscle regeneration in older population. Our earlier study demonstrated that zinc finger transcription factor early growth response 3 (Egr3) plays an important role for maintaining the number of myoblasts, suggesting that age-related decrease in muscle satellite cell should be associated with the expression levels of Egr3. The aim of this study was to investigate whether aging would alter the Egr3 expression in satellite cells. A couple groups of male C57BL/6J mice were examined in this study: young (3 Mo) and old (17 Mo). Immunohistochemical staining showed that the satellite cell number decreased in normal and injured muscles of old mice. In fluorescence-activated cell sorting-isolated muscle satellite cells from normal and injured muscles, the mRNA expression of Egr3 was significantly decreased with age regardless of injury. In harmony with these results, Pax7 mRNA levels also decreased in the satellite cells from old mice. Alternatively, inhibition of Egr3 expression by shRNA decreased Pax7 protein expression in cultured myoblasts. These results suggest that Egr3 is associated with the age-related decline of muscle satellite cells in older population. Also, Egr3 might be implicated in the regulation of Pax7. Therefore, the loss of Egr3 expression may elucidate attenuated MSCs function and muscle regeneration in older age.

Keywords: FACS; Myogenesis; Regeneration; Sarcopenia; Stem cells.

MeSH terms

  • Age Factors
  • Aging / genetics
  • Aging / metabolism*
  • Animals
  • Cells, Cultured
  • Early Growth Response Protein 3 / genetics*
  • Early Growth Response Protein 3 / metabolism
  • Gene Expression Regulation / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle Cells / metabolism
  • Muscle Development / physiology
  • Muscle, Skeletal / physiology
  • PAX7 Transcription Factor / genetics
  • PAX7 Transcription Factor / metabolism
  • Regeneration
  • Satellite Cells, Skeletal Muscle / metabolism*
  • Satellite Cells, Skeletal Muscle / physiology
  • Wound Healing

Substances

  • Egr3 protein, mouse
  • PAX7 Transcription Factor
  • Pax7 protein, mouse
  • Early Growth Response Protein 3