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Sci. Signal., 23 February 2010
Vol. 3, Issue 110, p. ra13
[DOI: 10.1126/scisignal.2000634]


Apoptotic Cells Activate the "Phoenix Rising" Pathway to Promote Wound Healing and Tissue Regeneration

Fang Li1, Qian Huang1,2,3, Jiang Chen4,5, Yuanlin Peng6, Dennis R. Roop4,5, Joel S. Bedford6, and Chuan-Yuan Li1,5,7*

1 Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
2 Center for Laboratory Research, First People’s Hospital, Shanghai Jiaotong University, Shanghai 200080, China.
3 National Laboratory for Oncogene and Related Genes Research, Cancer Institute of Shanghai Jiaotong University, Shanghai 200032, China.
4 Department of Dermatology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
5 Charles C. Gates Regenerative Medicine and Stem Cell Biology Program, University of Colorado School of Medicine, Aurora, CO 80045, USA.
6 Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA.
7 Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.

Abstract: The ability to regenerate damaged tissues is a common characteristic of multicellular organisms. We report a role for apoptotic cell death in promoting wound healing and tissue regeneration in mice. Apoptotic cells released growth signals that stimulated the proliferation of progenitor or stem cells. Key players in this process were caspases 3 and 7, proteases activated during the execution phase of apoptosis that contribute to cell death. Mice lacking either of these caspases were deficient in skin wound healing and in liver regeneration. Prostaglandin E2, a promoter of stem or progenitor cell proliferation and tissue regeneration, acted downstream of the caspases. We propose to call the pathway by which executioner caspases in apoptotic cells promote wound healing and tissue regeneration in multicellular organisms the "phoenix rising" pathway.

* To whom correspondence should be addressed. E-mail: Chuan.Li{at}

Citation: F. Li, Q. Huang, J. Chen, Y. Peng, D. R. Roop, J. S. Bedford, C.-Y. Li, Apoptotic Cells Activate the "Phoenix Rising" Pathway to Promote Wound Healing and Tissue Regeneration. Sci. Signal. 3, ra13 (2010).

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