Vascular endothelial growth factor promotes cardiomyocyte differentiation of embryonic stem cells
Vascular endothelial growth factor promotes cardiomyocyte differentiation of embryonic stem cells
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DOI：
10.1152/ajpheart.00363.2005
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发表时间：
2006-10-01
影响因子：
4.8
通讯作者：
Morgan, James P.
中科院分区：
文献类型：
--
作者：
Chen, Yu;Amende, Ivo;Morgan, James P.
血管内皮生长因子促进胚胎干细胞向心肌细胞分化。美国生理学杂志心脏循环生理学291：H1653-H1658，2006年。首次发表于2006年5月12日; doi：10.1152/ajpheart. 00363.2005. - 过表达血管内皮生长因子（VEGF）的胚胎干细胞（ESC）通过尚不清楚的机制改善心肌缺血和梗死小鼠模型的心脏功能。本实验研究了VEGF对体外培养的小鼠胚胎干细胞向心肌细胞分化的影响。我们使用流式细胞术来确定α-肌球蛋白重链（α-MHC），心肌肌钙蛋白I（cTn-I）和Nkx2.5在分化的ESC中的表达。VEGF（20 ng/ml）显著增强分化的ESCs中α-MHC、cTn-I和Nkx2.5的表达。Western blot分析证实了这些发现。我们发现VEGF受体FMS样酪氨酸激酶-1（Flt-1）和胎肝激酶-1（Flk-1）在ESC分化过程中表达增加。抗Flk-1抗体完全阻断VEGF诱导的NKx2.5阳性染色细胞，抗Flt-1抗体部分阻断VEGF诱导的NKx2.5阳性染色细胞。ERK抑制剂PD-098059消除VEGF诱导的ESCs心肌细胞分化。我们的研究结果表明，VEGF促进心肌细胞分化主要是通过ERK介导的Flk-1激活，并在较小程度上，通过Flt-1激活。这些发现可能对干细胞和生长因子疗法再生衰竭的心肌细胞具有重要意义。
Vascular endothelial growth factor promotes cardiomyocyte differentiation of embryonic stem cells. Am J Physiol Heart Circ Physiol 291: H1653-H1658, 2006. First published May 12, 2006; doi: 10.1152/ajpheart. 00363.2005. - Embryonic stem cells (ESCs) overexpressing the vascular endothelial growth factor (VEGF) improve cardiac function in mouse models of myocardial ischemia and infarction by mechanisms that are poorly understood. Here we studied the effects of VEGF on cardiomyocyte differentiation of mouse ESCs in vitro. We used flow cytometry to determine the expression of alpha-myosin heavy chain (alpha-MHC), cardiac troponin I (cTn-I), and Nkx2.5 in differentiated ESCs. VEGF (20 ng/ml) significantly enhanced alpha-MHC, cTn-I, and Nkx2.5 expression in differentiated ESCs. Western blot analysis confirmed these findings. We found that VEGF receptor FMS-like tyrosine kinase-1 (Flt-1) and fetal liver kinase-1 (Flk-1) expression increased during ESC differentiation. Antibodies against Flk-1 totally blocked and against Flt-1 partially blocked VEGF-induced NKx2.5-positive-stained cells. The ERK inhibitor PD-098059 abolished VEGF-induced cardiomyocyte differentiation of ESCs. Our results suggest that VEGF promotes cardiomyocyte differentiation predominantly by ERK-mediated Flk-1 activation and, to a lesser extent, by Flt-1 activation. These findings may be of significance for stem cell and growth factor therapies to regenerate failing cardiomyocytes.