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

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

来源：Developmental Cell, 2014, 31(6): 722-733.

DOI：10.1016/j.devcel.2014.11.012

• CELLULAR SENESCENCE
• IN-VIVO
• GROWTH-FACTOR
• TUMOR SUPPRESSION
• LIVER FIBROSIS
• TISSUE-REPAIR
• CANCER
• EXPRESSION
• BIOMARKER
• FIBROBLASTS

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.

• 出版日期2014-12-22