An essential role for senescent cells in optimal wound healing through secretion of PDGF-AADemaria, M., Ohtani, N., Youssef, S. A., Rodier, F., Toussaint, W., Mitchell, J. R., Laberge, R-M., Vijg, J., Van Steeg, H., Dollé, M. E. T., Hoeijmakers, J. H. J., de Bruin, A., Hara, E. & Campisi, J., 22-Dec-2014, In : Developmental Cell. 31, 6, p. 722-33 12 p.
Research output: Contribution to journal › Article › Academic › peer-review
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.
|Number of pages||12|
|Publication status||Published - 22-Dec-2014|
- Animals, Apoptosis, Cell Aging, Cell Differentiation, Endothelial Cells, Female, Fibroblasts, Luminescence, Male, Mesoderm, Mice, Mice, Transgenic, Myofibroblasts, Platelet-Derived Growth Factor, Transgenes, Wound Healing