Tenascin-C-EGFR activation induces functional human satellite cell proliferation and promotes wound-healing of skeletal muscles via oleanic acid

Dev Biol. 2023 Dec:504:86-97. doi: 10.1016/j.ydbio.2023.09.010. Epub 2023 Sep 26.

Abstract

Human satellite cells (HuSCs) have been deemed to be the potential cure to treat muscular atrophy diseases such as Duchenne muscular dystrophy. However, the clinical trials of HuSCs were restricted to the inadequacy of donors because of that freshly isolated HuSCs quickly lost the Pax7 expression and myogenesis capacity in vivo after a few days of culture. Here we found that oleanic acid, a kind of triterpenoid endowed with diverse biological functions with treatment potential, could efficiently promote HuSCs proliferation. The HuSCs cultured in the medium supplement with oleanic acid could maintain a high expression level of Pax7 and retain the ability to differentiate into myotubes as well as facilitate muscle regeneration in injured muscles of recipient mice. We further revealed that Tenascin-C acts as the core mechanism to activate the EGFR signaling pathway followed by HuSCs proliferation. Taken together, our data provide an efficient method to expand functional HuSCs and a novel mechanism that controls HuSCs proliferation, which sheds light on the HuSCs-based therapy to treat muscle diseases.

Keywords: Cell proliferation; EGFR; HuSCs; Oleanic acid; Tenascin-C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • ErbB Receptors / metabolism
  • Humans
  • Mice
  • Muscle, Skeletal / physiology
  • Satellite Cells, Skeletal Muscle* / physiology
  • Stem Cells
  • Tenascin* / metabolism

Substances

  • EGFR protein, human
  • ErbB Receptors
  • Tenascin
  • TNC protein, human