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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, etc.

Dev Cell. 2014 Dec 22;31(6):722-33.

PMID: 25499914

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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
IAR42413774 PDGF-AA from mouse PDGF-AA from mouse Price
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