Apoptotic cells activate the "phoenix rising" pathway to promote wound healing and tissue regeneration.
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 E(2), 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.
Li
Fang
F
Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Huang
Qian
Q
Chen
Jiang
J
Peng
Yuanlin
Y
Roop
Dennis R
DR
Bedford
Joel S
JS
Li
Chuan-Yuan
CY
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016718:Arachidonic Acid / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism*; D053179:Caspase 7 / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D017931:DNA Primers / Q000235:genetics; D015232:Dinoprostone / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D008115:Liver Regeneration / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D054467:Phospholipases A2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000502:physiology; D014945:Wound Healing / Q000502:physiology*
D017931:DNA Primers; D016718:Arachidonic Acid; D054467:Phospholipases A2; D053148:Caspase 3; D053179:Caspase 7; D015232:Dinoprostone