Periostin is essential for cardiac healing after acute myocardial infarction.
Periostin is essential for cardiac healing after acute myocardial infarction.
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DOI：
10.1084/jem.20071297
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发表时间：
2008-02-18
期刊：
影响因子：
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通讯作者：
Kudo A
中科院分区：
文献类型：
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作者：
Shimazaki M;Nakamura K;Kii I;Kashima T;Amizuka N;Li M;Saito M;Fukuda K;Nishiyama T;Kitajima S;Saga Y;Fukayama M;Sata M;Kudo A
急性心肌梗死（AMI）是一种常见的致死性心脏病，成纤维细胞向梗死区募集对于心脏愈合过程至关重要。尽管梗死心肌细胞外基质的硬度与心脏愈合有关，但心脏愈合的分子机制尚不完全清楚。我们发现，骨膜蛋白是一种基质细胞蛋白，在AMI后心脏愈合过程中起重要作用。人和小鼠AMI心肌梗死边界均有丰富的骨膜蛋白表达。我们生成了periostin - / -小鼠，没有发现形态学异常的心肌细胞表型；然而，AMI后，这些小鼠的心脏愈合受损，由于α平滑肌肌动蛋白阳性细胞数量减少，胶原纤维形成受损，FAK磷酸化降低，导致心肌硬度降低，导致心脏破裂。这些表型是通过剪接形式的骨膜蛋白的基因转移来挽救的。此外，FAK或αv-整合素抑制了骨膜蛋白促进的细胞迁移，表明αv-整合素、FAK和Akt参与了骨膜蛋白信号传导。我们的新发现表明，骨膜素通过fak -整合素信号对活化的成纤维细胞的募集有影响，并对AMI后愈合特异性的胶原纤维形成有影响。
Acute myocardial infarction (AMI) is a common and lethal heart disease, and the recruitment of fibroblastic cells to the infarct region is essential for the cardiac healing process. Although stiffness of the extracellular matrix in the infarct myocardium is associated with cardiac healing, the molecular mechanism of cardiac healing is not fully understood. We show that periostin, which is a matricellular protein, is important for the cardiac healing process after AMI. The expression of periostin protein was abundant in the infarct border of human and mouse hearts with AMI. We generated periostin −/− mice and found no morphologically abnormal cardiomyocyte phenotypes; however, after AMI, cardiac healing was impaired in these mice, resulting in cardiac rupture as a consequence of reduced myocardial stiffness caused by a reduced number of α smooth muscle actin–positive cells, impaired collagen fibril formation, and decreased phosphorylation of FAK. These phenotypes were rescued by gene transfer of a spliced form of periostin. Moreover, the inhibition of FAK or αv-integrin, which blocked the periostin-promoted cell migration, revealed that αv-integrin, FAK, and Akt are involved in periostin signaling. Our novel findings show the effects of periostin on recruitment of activated fibroblasts through FAK-integrin signaling and on their collagen fibril formation specific to healing after AMI.