期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 21, 期 8, 页码 1648-1655出版社
WILEY
DOI: 10.1111/jcmm.13078
关键词
exercise; proliferation; 5-fluorouracil; ischaemia/reperfusion injury
资金
- National Natural Science Foundation of China [81570362, 81200169, 91639101, 81470515, 81270314, 81472158, 81541007, 81400647]
- Innovation Program of Shanghai Municipal Education Commission [13YZ014]
- Innovation fund from Shanghai University [sdcx2012038]
- Program for the integration of production, teaching and research for University Teachers - Shanghai Municipal Education Commission
- Natural Science Foundation of Shanghai
- Shanghai Medical Guide Project from Shanghai Science and Technology Committee [134119a3000]
- development fund for Shanghai talents
The adult heart retains a limited ability to regenerate in response to injury. Although exercise can reduce cardiac ischaemia/reperfusion (I/R) injury, the relative contribution of cardiac cell proliferation including newly formed cardiomyocytes remains unclear. A 4-week swimming murine model was utilized to induce cardiac physiological growth. Simultaneously, the antineoplastic agent 5-fluorouracil (5-FU), which acts during the S phase of the cell cycle, was given to mice via intraperitoneal injections. Using EdU and Ki-67 immunolabelling, we showed that exercise-induced cardiac cell proliferation was blunted by 5-FU. In addition, the growth of heart in size and weight upon exercise was unaltered, probably due to the fact that exercise-induced cardiomyocyte hypertrophy was not influenced by 5-FU as demonstrated by wheat germ agglutinin staining. Meanwhile, the markers for pathological hypertrophy, including ANP and BNP, were not changed by either exercise or 5-FU, indicating that physiological growth still developed in the presence of 5-FU. Furthermore, we showed that CITED4, a key regulator for cardiomyocyte proliferation, was blocked by 5-FU. Meanwhile, C/EBP beta, a transcription factor responsible for both cellular proliferation and hypertrophy, was not altered by treatment with 5-FU. Importantly, the effects of exercise in reducing cardiac I/R injury could be abolished when cardiac cell proliferation was attenuated in mice treated with 5-FU. In conclusion, cardiac cell proliferation is not necessary for exercise-induced cardiac physiological growth, but it is required for exercise-associated protection against I/R injury.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据