Correlation between antizyme 1 and differentiation of vascular smooth muscle cells cultured in honeycomb-like type-I collagen matrix
Correlation between antizyme 1 and differentiation of vascular smooth muscle cells cultured in honeycomb-like type-I collagen matrix
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抗酶1与蜂窝状I型胶原基质中培养的血管平滑肌细胞分化的相关性
DOI：
10.1007/s00726-011-1034-8
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发表时间：
2012
期刊：
影响因子：
3.5
通讯作者：
et al
中科院分区：
文献类型：
--
作者：
Ishii;I.;et al
血管平滑肌细胞（SMC）在平板上培养时能够增殖，但在三维I型胶原基质（蜂窝）中维持时分化。由于抗酶1（AZ 1），鸟氨酸脱羧酶（ODC）和多胺吸收的负调节剂的存在下，生长在蜂窝中的SMC含有低水平的多胺。为了阐明AZ 1在蜂窝SMC分化中的作用，将ODC基因稳定转染到SMC中（ODC-SMC）。尽管ODC-SMC在平板上的增殖加速，磷酸化的粘着斑激酶（FAK）增加，α-肌动蛋白和肌球蛋白（α-actin和myosin，分化标志蛋白）减少，但ODC-SMC在蜂窝状结构中的生长停止，与正常SMC相似，磷酸化FAK水平低，α-actin和myosin水平高。AZ 1在ODC-SMC中的表达在平板上较低，而在蜂窝中较高。抗酶剂不仅降低了ODC水平，而且抑制了多胺摄取活性。这些结果共同表明，在蜂窝SMC中由AZ 1引起的低水平多胺抑制FAK的磷酸化并增强α-肌动蛋白和肌球蛋白的表达，从而通过抑制粘着斑而导致分化。
Vascular smooth muscle cells (SMC) are able to proliferate when cultured on plates, but become differentiated when maintained in three-dimensional type I collagen matrices (honeycombs). SMC grown in honeycombs contained a low level of polyamines due to the presence of antizyme 1 (AZ1), a negative regulator of ornithine decarboxylase (ODC) and of polyamine uptake. To clarify the role of AZ1 in differentiation of SMC in honeycombs, an ODC gene was stably transfected into SMC (ODC-SMC). Although proliferation of ODC-SMC on plates was accelerated together with an increase in phosphorylated focal adhesion kinase (FAK) and a decrease in α-actin and myosin, maker proteins of differentiation, growth of ODC-SMC ceased in honeycombs similarly to normal SMC with a low level of phosphorylated FAK and a high level of α-actin and myosin. AZ1 expression in ODC-SMC on plates was low, but that in honeycombs was high. Antizyme in ODC-SMC in honeycombs not only decreased the level of ODC but also inhibited polyamine uptake activity. These results taken together suggest that low levels of polyamines caused by AZ1 in SMC in honeycombs inhibit phosphorylation of FAK and enhance expression of α-actin and myosin, resulting in differentiation through inhibition of focal adhesions.