Cardiac endothelial cells express Wilms' tumor-1 Wt1 expression in the developing, adult and infarcted heart
Cardiac endothelial cells express Wilms' tumor-1 Wt1 expression in the developing, adult and infarcted heart
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DOI：
10.1016/j.yjmcc.2015.02.007
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发表时间：
2015-04-01
影响因子：
5
通讯作者：
Kruithof, Boudewijn P. T.
中科院分区：
文献类型：
--
作者：
Duim, Sjoerd N.;Kurakula, Kondababu;Kruithof, Boudewijn P. T.
心肌梗死是世界范围内的主要死亡原因。由于其有限的再生能力，丧失的心肌细胞被非收缩性纤维化瘢痕组织取代。心脏的心外膜层在发育期间提供心脏祖细胞。由于这一层在心脏损伤后的成年心脏中恢复了胚胎特征，因此它可以作为常驻心脏祖细胞的有希望的来源。肾母细胞瘤-1（Wt 1）与心外膜的激活和再激活有关，因此对心外膜的分化和再生能力具有潜在的重要性。为了更深入地了解WO的调节，我们研究了Wt 1在小鼠发育过程中和心脏损伤后的时空表达模式。有趣的是，我们发现Wt 1在E12.5以后发育心脏的心肌心室层内的大多数心脏内皮细胞中表达。在成人心脏中，只有冠状动脉内皮细胞的一个子集保持Wt 1阳性。心肌梗死后，Wt 1在梗死区和心脏边缘区的内皮细胞中暂时上调。体外实验表明，缺氧可诱导内皮Wt 1表达。我们发现，Wt 1与内皮细胞增殖：Wt 1的表达是在增殖的内皮细胞，Wt 1敲低抑制内皮细胞的增殖，Wt 1调节CyclinD 1的表达。最后，缺乏Wt 1的内皮细胞不能在体外建立适当的血管网络。总之，这些结果表明Wt 1在发育和疾病中的心脏血管形成中可能发挥作用。(C)2015爱思唯尔有限公司版权所有。
Myocardial infarction is the leading cause of death worldwide. Due to their limited regenerative capacity lost cardiomyocytes are replaced by a non-contractile fibrotic scar tissue. The epicardial layer of the heart provides cardiac progenitor cells during development. Because this layer regains embryonic characteristics in the adult heart after cardiac injury, it could serve as a promising source for resident cardiac progenitor cells. Wilms' tumor-1 (Wt1) is associated with the activation and reactivation of the epicardium and therefore potentially important for the differentiation and regenerative capacity of the epicardium. To gain more insight into the regulation of WO we examined the spatiotemporal expression pattern of Wt1 during murine development and after cardiac injury. Interestingly, we found that Wt1 is expressed in the majority of the cardiac endothelial cells within the myocardial ventricular layer of the developing heart from E12.5 onwards. In the adult heart only a subset of coronary endothelial cells remains positive for Wt1. After myocardial infarction Wt1 is temporally upregulated in the endothelial cells of the infarcted area and the border zone of the heart In vitro experiments show that endothelial Wt1 expression can be induced by hypoxia. We show that Wt1 is associated with endothelial cell proliferation: Wt1 expression is higher in proliferating endothelial cells, Wt1 knockdown inhibits the proliferation of endothelial cells, and Wt1 regulates CyclinD1 expression. Finally, endothelial cells lacking Wt1 are not capable to establish a proper vascular network in vitro. Together, these results suggest a possible role for Wt1 in cardiac vessel formation in development and disease. (C) 2015 Elsevier Ltd. All rights reserved.