Hsueh Ying-Chang, Wu Jasmine M F, Yu Chun-Keung, Wu Kenneth K, Hsieh Patrick C H
Institute of Basic Medical Sciences, National Cheng Kung University and Hospital, Tainan, Taiwan.
EMBO Mol Med. 2014 Apr;6(4):496-503. doi: 10.1002/emmm.201303687. Epub 2014 Jan 21.
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.
尽管已有报道称成年哺乳动物心脏具有自我更新能力，但目前已知的促进损伤后心肌细胞再生的药物治疗方法却很少。在本研究中，我们证明了干细胞/祖细胞介导的心肌细胞补充的关键时期在梗死发生后7天内开始，并在第10天达到饱和。此外，用COX-2抑制剂阻断炎症反应也可能降低内源性干细胞/祖细胞重新填充丢失细胞的能力。注射COX-2产物PGE2可增强幼鼠的心肌细胞补充，并通过减弱老年小鼠体内的TGF-β1信号传导来恢复细胞更新。进一步分析表明，心脏干细胞对PGE2有反应，并且PGE2可能通过EP2受体直接调节干细胞活性，或通过在体内调节其微环境间接调节干细胞活性。我们的研究结果提供了证据，表明PGE2在心脏再生方面具有巨大潜力。
