期刊
CARDIOVASCULAR RESEARCH
卷 113, 期 6, 页码 620-632出版社
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvx001
关键词
Periostin; Myocardial regeneration; Glycogen synthase kinase 3 beta; Cyclin D1; Myocardial infarction
资金
- National Natural Science Foundation of China [31271513]
- Municipal Planning Projects of Scientific Technology of Guangzhou [20150401001]
- Provincial Natural Science Foundation of Guangdong [2014A030313342, 2015A030313301, 2015A030313298]
To resolve the controversy as to whether periostin plays a role in myocardial regeneration after myocardial infarction (MI), we created a neonatal mouse model of MI to investigate the influence of periostin ablation on myocardial regeneration and clarify the underlying mechanisms. Neonatal periostin-knockout mice and their wildtype littermates were subjected to MI or sham surgery. In the wildtype mice after MI, fibrosis was detectable at 3 days and fibrotic tissue was completely replaced by regenerated myocardium at 21 days. In contrast, in the knockout mice, significant fibrosis in the infarcted area was present at even 3 weeks after MI. Levels of phosphorylated-histone 3 and aurora B in the myocardium, detected by immunofluorescence and western blotting, were significantly lower in knockout than in wildtype mice at 7 days after MI. Similarly, angiogenesis was decreased in the knockout mice after MI. Expression of both the endothelial marker CD-31 and alpha-smooth muscle actin was markedly lower in the knockout than in wildtype mice at 7 days after MI. The knockout MI group had elevated levels of glycogen synthase kinase (GSK) 3 beta and decreased phosphatidylinositol 3-kinase (PI3K), phosphorylated serine/threonine protein kinase B (p-Akt), and cyclin D1, compared with the wildtype MI group. Similar effects were observed in experiments using cultured cardiomyocytes from neonatal wildtype or periostin knockout mice. Administration of SB216763, a GSK3 beta inhibitor, to knockout neonatal mice decreased myocardial fibrosis and increased angiogenesis in the infarcted area after MI. Ablation of periostin suppresses post-infarction myocardial regeneration by inhibiting the PI3K/GSK3 beta/cyclin D1 signalling pathway, indicating that periostin is essential for myocardial regeneration.
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