[PMID]: | 28453729 |
[Au] Autor: | Chen Z; Xie J; Hao H; Lin H; Wang L; Zhang Y; Chen L; Cao S; Huang X; Liao W; Bin J; Liao Y |
[Ad] Endereço: | State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838, Guangzhou Avenue North, Guangzhou 510515, China. |
[Ti] Título: | Ablation of periostin inhibits post-infarction myocardial regeneration in neonatal mice mediated by the phosphatidylinositol 3 kinase/glycogen synthase kinase 3ß/cyclin D1 signalling pathway. |
[So] Source: | Cardiovasc Res;113(6):620-632, 2017 May 01. |
[Is] ISSN: | 1755-3245 |
[Cp] País de publicação: | England |
[La] Idioma: | eng |
[Ab] Resumo: | 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 α-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) 3ß 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 GSK3ß 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/GSK3ß/cyclin D1 signalling pathway, indicating that periostin is essential for myocardial regeneration. |
[Mh] Termos MeSH primário: |
Moléculas de Adesão Celular/deficiência Ciclina D1/metabolismo Infarto do Miocárdio/enzimologia Miocárdio/enzimologia Fosfatidilinositol 3-Quinase/metabolismo Regeneração Proteínas Repressoras/metabolismo Transdução de Sinais
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[Mh] Termos MeSH secundário: |
Animais Animais Recém-Nascidos Moléculas de Adesão Celular/genética Células Cultivadas Modelos Animais de Doenças Fibrose Camundongos Knockout Infarto do Miocárdio/genética Infarto do Miocárdio/patologia Infarto do Miocárdio/fisiopatologia Miocárdio/patologia Neovascularização Fisiológica Fosforilação Inibidores de Proteínas Quinases/farmacologia Proteínas Proto-Oncogênicas c-akt/metabolismo Regeneração/efeitos dos fármacos Proteínas Repressoras/antagonistas & inibidores Transdução de Sinais/efeitos dos fármacos Fatores de Tempo
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Ccnd1 protein, mouse); 0 (Cell Adhesion Molecules); 0 (GSKIP protein, mouse); 0 (Postn protein, mouse); 0 (Protein Kinase Inhibitors); 0 (Repressor Proteins); 136601-57-5 (Cyclin D1); EC 2.7.1.137 (Phosphatidylinositol 3-Kinase); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) |
[Em] Mês de entrada: | 1802 |
[Cu] Atualização por classe: | 180308 |
[Lr] Data última revisão:
| 180308 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170429 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1093/cvr/cvx001 |
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