An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA

Marco Demaria, Naoko Ohtani, Sameh A Youssef, Francis Rodier, Wendy Toussaint, James R Mitchell, Remi-Martin Laberge, Jan Vijg, Harry Van Steeg, Martijn E T Dollé, Jan H J Hoeijmakers, Alain de Bruin, Eiji Hara, Judith Campisi

OnderzoeksoutputAcademicpeer review

697 Citaten (Scopus)
71 Downloads (Pure)

Samenvatting

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.

Originele taal-2English
Pagina's (van-tot)722-733
Aantal pagina's12
TijdschriftDevelopmental Cell
Volume31
Nummer van het tijdschrift6
DOI's
StatusPublished - 22-dec-2014

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