Overexpression of cas-interacting zinc finger protein (CIZ) suppresses proliferation and enhances expression of type I collagen gene in osteoblast-like MC3T3E1 cells
Overexpression of cas-interacting zinc finger protein (CIZ) suppresses proliferation and enhances expression of type I collagen gene in osteoblast-like MC3T3E1 cells
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DOI：
10.1006/excr.2000.5051
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发表时间：
2000-12-15
影响因子：
3.7
通讯作者：
Noda, M
中科院分区：
文献类型：
--
作者：
Furuya, K;Nakamoto, T;Noda, M
成骨细胞是指在激素和细胞因子的调控下，细胞外基质分子通过附着而形成骨的细胞。为了深入了解细胞内信号分子在介导成骨细胞功能附着相关调节中的作用，我们在成骨细胞样MC3T3E1细胞中研究了与p130(Cas)相互作用的一种新的信号蛋白CIZ过表达的影响。在MC3T3E1细胞中，CIZ基因呈结构性表达，内源性CIZ基因定位于细胞在纤维连接蛋白、胶原蛋白或牛血清白蛋白载体上较高聚集的附着部位。与空载体转染组相比，CIZ基因过表达增加了细胞黏附斑块的数量，抑制了细胞的增殖，而且，CIZ基因过表达促进了成骨细胞主要产物、骨基质中含量最高的I型胶原基因的表达。对I型胶原基因启动子区域的分析证实，存在一个共同的CIZ结合序列，这确实赋予了异源启动子对CIZ过度表达的反应性。这些数据表明，CIZ在控制成骨细胞功能方面是一种新的调节分子，(C)2000学术出版社。
Osteoblasts are the cells which form bone under the regulation not only by hormones and cytokines but also by ECM molecules via their attachment. To obtain insights into the role of intracellular signaling molecules operating to mediate the attachment-related regulation of osteoblastic functions, we investigated in osteoblast-like MC3T3E1 cells the effects of the overexpression of CIZ, a novel signaling protein which interacts with p130(Cas). In MC3T3E1 cells, CIZ mRNA is expressed constitutively, Endogenous CIZ was localized in the MC3T3E1 cells with relatively high levels of accumulation at the attachment sites when the cells were cultured on fibronectin, collagen, or BSA CIZ overexpression increased the number of adhesion plaques and reduced proliferation of the cells compared to that of control cells transfected with an empty vector, Furthermore, CIZ overexpression enhanced type I collagen mRNA expression, the most abundant constituent of bone matrix and a major product of osteoblasts. Analysis of the promoter region of type I collagen gene identified the presence of a consensus CIZ-binding sequence, which indeed conferred responsiveness to CIZ overexpression to a heterologous promoter. These data indicate that CIZ acts as a novel regulatory molecule in controlling osteoblastic function, (C) 2000 Academic Press.