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

Marco Demaria, Naoko Ohtani, SamehA Youssef, Francis Rodier, Wendy Toussaint, JamesR Mitchell, Remi Martin Laberge, Jan Vijg, Harry VanSteeg, MartijnE T. Dollé, JanH J. Hoeijmakers, Alain deBruin, Eiji Hara, Judith Campisi

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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 amouse model in which senescent cells can be visualized and eliminated in living animals. We show thatsenescent 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). Intwo 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.

Original languageEnglish (US)
Pages (from-to)722-733
Number of pages12
JournalDevelopmental Cell
Volume31
Issue number6
DOIs
StatePublished - Dec 22 2014

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Platelet-Derived Growth Factor
Wound Healing
Cells
Phenotype
Myofibroblasts
Endothelial cells
Wounds and Injuries
Pathology
Fibroblasts
Animals
Repair
Tissue
Cell Aging
Endothelial Cells
Skin
Growth
Neoplasms

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Demaria, M., Ohtani, N., Youssef, S., Rodier, F., Toussaint, W., Mitchell, J., ... Campisi, J. (2014). An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Developmental Cell, 31(6), 722-733. https://doi.org/10.1016/j.devcel.2014.11.012

An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. / Demaria, Marco; Ohtani, Naoko; Youssef, SamehA; Rodier, Francis; Toussaint, Wendy; Mitchell, JamesR; Laberge, Remi Martin; Vijg, Jan; VanSteeg, Harry; Dollé, MartijnE T.; Hoeijmakers, JanH J.; deBruin, Alain; Hara, Eiji; Campisi, Judith.

In: Developmental Cell, Vol. 31, No. 6, 22.12.2014, p. 722-733.

Research output: Contribution to journalArticle

Demaria, M, Ohtani, N, Youssef, S, Rodier, F, Toussaint, W, Mitchell, J, Laberge, RM, Vijg, J, VanSteeg, H, Dollé, MT, Hoeijmakers, JJ, deBruin, A, Hara, E & Campisi, J 2014, 'An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA', Developmental Cell, vol. 31, no. 6, pp. 722-733. https://doi.org/10.1016/j.devcel.2014.11.012
Demaria M, Ohtani N, Youssef S, Rodier F, Toussaint W, Mitchell J et al. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Developmental Cell. 2014 Dec 22;31(6):722-733. https://doi.org/10.1016/j.devcel.2014.11.012
Demaria, Marco ; Ohtani, Naoko ; Youssef, SamehA ; Rodier, Francis ; Toussaint, Wendy ; Mitchell, JamesR ; Laberge, Remi Martin ; Vijg, Jan ; VanSteeg, Harry ; Dollé, MartijnE T. ; Hoeijmakers, JanH J. ; deBruin, Alain ; Hara, Eiji ; Campisi, Judith. / An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. In: Developmental Cell. 2014 ; Vol. 31, No. 6. pp. 722-733.
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