Ishii I, Tomizawa A, Kawachi H, Suzuki T, Kotani A, Koshushi I, Itoh H, Morisaki N, Bujo H, Saito Y, Ohmori S, Kitada M
Faculty of Pharmaceutical Sciences, Chiba University, 1-33, Yayoi-cho, Inageku, Chiba 263-8522, Japan.
Atherosclerosis. 2001 Oct;158(2):377-84. doi: 10.1016/s0021-9150(01)00461-0.
Vascular smooth muscle cells (SMCs) undergo phenotype change with the development of atherosclerosis. The phenotype changes of SMCs have been observed in various culture conditions, such as collagen-coated dishes. Here, we report the morphological and functional features of SMCs in a novel culture system using type I-collagen in a characteristic three-dimensional structure designated as honeycombs. The number of ribosome and mitochondria in SMCs cultured in honeycombs was one half or third of those cultured on collagen-coated plastic plates. DNA and protein synthesis of SMCs cultured in honeycombs were less than 1 and 30-40%, respectively, of those cultured on plastic plates. In addition, PDGF-BB did not increase the amount of DNA synthesis in SMCs in honeycombs. SMCs in honeycombs were shown to express several proteins, which are known to express in SMCs in medial layers of arteries. Particularly, caldesmon heavy chain was expressed in SMCs cultured in honeycombs, whereas not in those on plastic plates. Although focal adhesion kinase (FAK) was clearly detected in SMCs in honeycomb, the phosphotyrosine content of focal adhesion kin ase decreased in the process of culture. Immunoblot analysis showed dear different expression of ERK1 and ERK2 of mitogen-activated protein kinase in SMCs. SMCs in honeycombs expressed ERK2, more abundantly compared to ERK1, whereas SMCs in plates show the same levels of expressions for both proteins. Thus, the histological and functional feature of SMCs in the novel culture system is different from SMCs in plastic plates. The three-dimensional culture system described here may be indicating that cultured SMCs are able to express different proteins responding to the surrounding structures.
血管平滑肌细胞(SMCs)会随着动脉粥样硬化的发展而发生表型变化。在各种培养条件下,如胶原包被的培养皿中,已观察到SMCs的表型变化。在此,我们报告了在一种新型培养系统中SMCs的形态和功能特征,该系统使用具有蜂窝状特征三维结构的I型胶原蛋白。在蜂窝状结构中培养的SMCs中的核糖体和线粒体数量分别是在胶原包被的塑料板上培养的细胞的二分之一或三分之一。在蜂窝状结构中培养的SMCs的DNA和蛋白质合成分别不到在塑料板上培养的细胞的1%和30 - 40%。此外,血小板衍生生长因子BB(PDGF - BB)并未增加蜂窝状结构中SMCs的DNA合成量。蜂窝状结构中的SMCs显示出表达几种已知在动脉中层SMCs中表达的蛋白质。特别是,钙调蛋白重链在蜂窝状结构中培养的SMCs中表达,而在塑料板上培养的细胞中不表达。尽管在蜂窝状结构中的SMCs中清楚地检测到粘着斑激酶(FAK),但粘着斑激酶的磷酸酪氨酸含量在培养过程中下降。免疫印迹分析显示丝裂原活化蛋白激酶的ERK1和ERK2在SMCs中有明显不同的表达。蜂窝状结构中的SMCs比ERK1更大量地表达ERK2,而平板上的SMCs中这两种蛋白的表达水平相同。因此,新型培养系统中SMCs的组织学和功能特征与塑料板上的SMCs不同。这里描述的三维培养系统可能表明培养的SMCs能够根据周围结构表达不同的蛋白质。