The adhering junctions of valvular interstitial cells: molecular composition in fetal and adult hearts and the comings and goings of plakophilin-2 in situ, in cell culture and upon re-association with scaffolds
The adhering junctions of valvular interstitial cells: molecular composition in fetal and adult hearts and the comings and goings of plakophilin-2 in situ, in cell culture and upon re-association with scaffolds
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DOI：
10.1007/s00441-011-1315-2
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发表时间：
2012-05-01
影响因子：
3.6
通讯作者：
Franke, Werner Wilhelm
中科院分区：
文献类型：
--
作者：
Barth, Mareike;Rickelt, Steffen;Franke, Werner Wilhelm
心脏瓣膜间质细胞是哺乳动物心脏中最常见的细胞类型之一。为了为分离的瓣膜间质细胞(VICs)在细胞培养中的生长和用于再植入手术提供细胞和分子生物学基础，我们在原位和培养中检测了VICs在胎儿、出生后和成人心脏中与细胞外基质(ECM)材料和去细胞心脏瓣膜支架的重新结合。在所有四种哺乳动物(人、牛、猪和绵羊)中，连接VIC的典型的间叶型细胞-细胞黏附连接(AJ)表现为正常的N-钙粘附素点状粘附性。然而，它们的分子集合在不同的生长条件下会发生变化，因为亲板素-2(PKP2)是上皮桥粒的主要细胞质成分，在以促进增殖为特征的生长条件下，即在胎儿心脏瓣膜和细胞培养中，作为主要成分被招募并整合到VIC-AJ的斑块中。当PKP2重新种植到去细胞的心脏瓣膜上或在与人工支架相关的生长阶段时，PKP2在很大程度上从AJ中消失。随着最近在心脏粘液瘤和其他多种间叶性肿瘤的AJ中也检测到PKP2，当与ECM支架和去细胞心脏瓣膜重新结合时，PKP2恢复到正常的PKP2阴性状态，现在可能为培养的VICs用于瓣膜置换手术提供安全的基础。更令人惊讶的是，在不同的心内膜内皮细胞群中也观察到了这种类型的PKP2的瞬时获得，在那里它似乎对应于准备进行内皮-间充质转化(EMT)的细胞类型。
The interstitial cells of cardiac valves represent one of the most frequent cell types in the mammalian heart. In order to provide a cell and molecular biological basis for the growth of isolated valvular interstitial cells (VICs) in cell culture and for the use in re-implantation surgery we have examined VICs in situ and in culture, in fetal, postnatal and adult hearts, in re-associations with scaffolds of extracellular matrix (ECM) material and decellularized heart valves. In all four mammalian species examined (human, bovine, porcine and ovine), the typical mesenchymal-type cell-cell adherens junctions (AJs) connecting VICs appear as normal N-cadherin based puncta adhaerentia. Their molecular ensemble, however, changes under various growth conditions insofar as plakophilin-2 (Pkp2), known as a major cytoplasmic plaque component of epithelial desmosomes, is recruited to and integrated in the plaques of VIC-AJs as a major component under growth conditions characterized by enhanced proliferation, i.e., in fetal heart valves and in cell cultures. Upon re-seeding onto decellularized heart valves or in stages of growth in association with artificial scaffolds, Pkp2 is - for the most part - lost from the AJs. As Pkp2 has recently also been detected in AJs of cardiac myxomata and diverse other mesenchymal tumors, the demonstrated return to the normal Pkp2-negative state upon re-association with ECM scaffolds and decellularized heart valves may now provide a safe basis for the use of cultured VICs in valve replacement surgery. Even more surprising, this type of transient acquisition of Pkp2 has also been observed in distinct groups of endothelial cells of the endocardium, where it seems to correspond to the cell type ready for endothelial-mesenchymal transition (EMT).