| First Author | Chen Z | Year | 2017 |
| Journal | Cardiovasc Res | Volume | 113 |
| Issue | 6 | Pages | 620-632 |
| PubMed ID | 28453729 | Mgi Jnum | J:259008 |
| Mgi Id | MGI:6142814 | Doi | 10.1093/cvr/cvx001 |
| Citation | Chen Z, et al. (2017) Ablation of periostin inhibits post-infarction myocardial regeneration in neonatal mice mediated by the phosphatidylinositol 3 kinase/glycogen synthase kinase 3beta/cyclin D1 signalling pathway. Cardiovasc Res 113(6):620-632 |
| abstractText | Aims: 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. Methods and results: 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) 3beta 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 GSK3beta inhibitor, to knockout neonatal mice decreased myocardial fibrosis and increased angiogenesis in the infarcted area after MI. Conclusion: Ablation of periostin suppresses post-infarction myocardial regeneration by inhibiting the PI3K/GSK3beta/cyclin D1 signalling pathway, indicating that periostin is essential for myocardial regeneration. |
