Prostaglandin E2 promotes post‐infarction cardiomyocyte replenishment by endogenous stem cells

EMBO Molecular Medicine

Ying-Chang Hsueh²  Jasmine M F Wu²  Chun-Keung Yu²  Kenneth K Wu¹ 

[1] Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan;Institute of Basic Medical Sciences, National Cheng Kung University and Hospital, Tainan, Taiwan

关键词: aging;    cardiac regeneration;    cyclooxygenase 2;    genetic fate‐mapping;    inflammation;   

DOI  :  10.1002/emmm.201303687

来源: Wiley

【 摘 要 】

Abstract

Although self-renewal ability of adult mammalian heart has been reported, few pharmacological treatments are known to promote cardiomyocyte regeneration after injury. In this study, we demonstrate that the critical period of stem/progenitor cell-mediated cardiomyocyte replenishment is initiated within 7 days and saturates on day 10 post-infarction. Moreover, blocking the inflammatory reaction with COX-2 inhibitors may also reduce the capability of endogenous stem/progenitor cells to repopulate lost cells. Injection of the COX-2 product PGE₂ enhances cardiomyocyte replenishment in young mice and recovers cell renewal through attenuating TGF-β1 signaling in aged mice. Further analyses suggest that cardiac stem cells are PGE₂-responsive and that PGE₂ may regulate stem cell activity directly through the EP2 receptor or indirectly by modulating its micro-environment in vivo. Our findings provide evidence that PGE₂ holds great potential for cardiac regeneration.

Synopsis

Although lost cardiomyocytes could be replenished after injury, the efficiency is extremely low. Here, the authors show that PGE2 treatment at a critical time period improves stem cell-mediated cardiac repair in young mice and restores it in aged animals.

• Stem cell-derived cardiomyocyte replenishment occurs within 7 days of injury.
• An early inflammatory signal regulates cardiac regeneration after infarction.
• PGE2 stimulates cardiomyocyte replenishment mediated by cardiac stem cells.
• PGE2 rescues the cardiomyocyte replenishment capacity that is lost in aged mice.

【 授权许可】

CC BY   
© 2014 The Authors.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.