Thymosin β4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair
Thymosin β4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair
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DOI：
10.1038/nature03000
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发表时间：
2004-11-25
期刊：
影响因子：
64.8
通讯作者：
Srivastava, D
中科院分区：
文献类型：
--
作者：
Bock-Marquette, I;Saxena, A;Srivastava, D
心脏病是新生儿和成人死亡的主要原因。通过使用干细胞促进心脏修复的努力有希望，但通常涉及祖细胞的分离和引入。在这里，我们表明，G-肌动蛋白螯合肽胸腺素β 4促进心肌和内皮细胞迁移在胚胎心脏，并保留在出生后的心肌细胞的这一属性。胸腺素β 4也能提高胚胎和出生后心肌细胞的存活率。我们发现胸腺素β 4与PINCH和整合素连接激酶（ILK）形成功能复合物，导致存活激酶Akt（也称为蛋白激酶B）活化。在小鼠冠状动脉结扎后，胸腺素β 4治疗导致心脏中ILK和Akt活性的上调，增强了早期肌细胞存活并改善了心脏功能。这些发现表明，胸腺素β 4促进心肌细胞迁移，存活和修复，其调节的途径可能是急性心肌损伤的新治疗靶点。
Heart disease is a leading cause of death in newborn children and in adults. Efforts to promote cardiac repair through the use of stem cells hold promise but typically involve isolation and introduction of progenitor cells. Here, we show that the G-actin sequestering peptide thymosin beta4 promotes myocardial and endothelial cell migration in the embryonic heart and retains this property in postnatal cardiomyocytes. Survival of embryonic and postnatal cardiomyocytes in culture was also enhanced by thymosin beta4. We found that thymosin beta4 formed a functional complex with PINCH and integrin-linked kinase (ILK), resulting in activation of the survival kinase Akt ( also known as protein kinase B). After coronary artery ligation in mice, thymosin beta4 treatment resulted in upregulation of ILK and Akt activity in the heart, enhanced early myocyte survival and improved cardiac function. These findings suggest that thymosin beta4 promotes cardiomyocyte migration, survival and repair and the pathway it regulates may be a new therapeutic target in the setting of acute myocardial damage.