CD117-positive cells in adult human heart are localized in the subepicardium, and their activation is associated with laminin-1 and α6 integrin expression
CD117-positive cells in adult human heart are localized in the subepicardium, and their activation is associated with laminin-1 and α6 integrin expression
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DOI：
10.1634/stemcells.2007-0732
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发表时间：
2008-01-01
期刊：
影响因子：
5.2
通讯作者：
Montagnani, Stefania
中科院分区：
文献类型：
--
作者：
Castaldo, Clotilde;Di Meglio, Franca;Montagnani, Stefania
cd117阳性细胞在正常和病理状态下参与心脏细胞更新，最近在成人心脏中被描述。由于细胞外基质蛋白及其受体的精确时空表达对器官形成至关重要，我们比较了心肌原始cd117阳性细胞在成人正常和缺血性心肌病心脏中的分布，以及层粘胶蛋白和整合素同种异构体的定位和表达。病理心脏中cd117阳性细胞明显多于正常心脏。它们主要局限于心房，心内膜下的数量是心肌的38倍。与正常心脏相比，病理心脏心膜下cd117阳性细胞多数为α(6)整合素阳性。层粘连蛋白-1是发育中的心脏的典型特征，主要存在于成人心脏的心内膜下。免疫印迹显示其在正常心房和病理性左心室的表达最高。与对照组相比，两种层粘连蛋白异构体均减少了cd117阳性细胞的凋亡，增加了细胞的增殖和迁移，但层粘连蛋白1的作用明显优于层粘连蛋白2。经特异性小干扰RNA转染证实，α(6)整合素介导的信号传导与迁移和保护细胞凋亡有关。这些数据表明，心肌cd117阳性细胞数量的增加和laminin-1的表达在缺血性心肌病中观察到。心外膜下cd117阳性细胞的定位和层粘连蛋白-1和α(6)整合素亚基的表达都可能与最近在成人心脏中描述的涉及上皮-间质转化的再生激活相对应。
CD117-positive cells contributing to cardiac cell turnover in normal and pathological conditions have recently been described in adult human heart. Since the precise spatial and temporal expression of extracellular matrix proteins and their receptors is critical for organ formation, we compared the distribution of cardiac primitive CD117-positive cells in the human adult normal and pathological hearts with ischemic cardiomyopathy, with respect to localization and expression of laminin and integrin isoforms. In the pathological hearts, CD117-positive cells were significantly more numerous than in the normal hearts. They were localized mainly in the atria and were up to 38-fold more numerous in the subepicardium than in the myocardium. Compared with normal hearts, most CD117-positive cells in the subepicardium of pathological hearts were alpha(6) integrin-positive. Laminin-1, typical of developing heart, was found predominantly in the subepicardium of adult heart. Immunoblotting revealed its highest expression in the normal atrium and pathological left ventricle. Both laminin isoforms reduced apoptosis and increased proliferation and migration of CD117-positive cells in vitro with respect to control, but the effects of laminin-1 significantly outweighed those of laminin-2. Signaling mediated by alpha(6) integrin was implicated in the migration and protection from apoptosis, as documented by transfection with specific small interfering RNA. These data reveal that the increase in the number of cardiac CD117-positive cells and the expression of laminin-1 are observed in ischemic cardiomyopathy. Subepicardial localization of CD117-positive cells and expression of laminin-1 and alpha(6) integrin subunits may all correspond to the activation of regeneration involving an epithelial-mesenchymal transition recently described in adult heart.