An Essential Role for Senescent Cells in Optimal Wound Healing Through Secretion of PDGF-AA

Dev Cell. 2014 Dec 22;31(6):722-33. doi: 10.1016/j.devcel.2014.11.012. Epub 2014 Dec 11.

Abstract

Cellular senescence suppresses cancer by halting the growth of premalignant cells, yet the accumulation of senescent cells is thought to drive age-related pathology through a senescence-associated secretory phenotype (SASP), the function of which is unclear. To understand the physiological role(s) of the complex senescent phenotype, we generated a mouse model in which senescent cells can be visualized and eliminated in living animals. We show that senescent fibroblasts and endothelial cells appear very early in response to a cutaneous wound, where they accelerate wound closure by inducing myofibroblast differentiation through the secretion of platelet-derived growth factor AA (PDGF-AA). In two mouse models, topical treatment of senescence-free wounds with recombinant PDGF-AA rescued the delayed wound closure and lack of myofibroblast differentiation. These findings define a beneficial role for the SASP in tissue repair and help to explain why the SASP evolved.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis
  • Cell Differentiation
  • Cellular Senescence*
  • Endothelial Cells / cytology*
  • Female
  • Fibroblasts / metabolism
  • Luminescence
  • Male
  • Mesoderm / cytology*
  • Mice
  • Mice, Transgenic
  • Myofibroblasts / metabolism
  • Platelet-Derived Growth Factor / chemistry
  • Platelet-Derived Growth Factor / metabolism*
  • Transgenes
  • Wound Healing*

Substances

  • Platelet-Derived Growth Factor
  • platelet-derived growth factor A