Microarray analysis of the effect of dexamethasone on murine cochlear explants.

Microarray analysis of the effect of dexamethasone on murine cochlear explants.
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DOI:
10.3109/00016489.2010.498836
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发表时间:
2010-12
影响因子:
1.4
通讯作者:
Nishizaki K
Nishizaki K
中科院分区:
医学4区
文献类型:
--
作者:
Maeda Y;Fukushima K;Hirai M;Kariya S;Smith RJ;Nishizaki K

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微阵列分析确定了地塞米松在小鼠耳蜗组织培养组织中上调或下调的39个基因。在受影响最严重的八个基因中,有几个基因被认为在受伤的内耳中具有保护作用[FKBP5,糖皮质激素诱导的亮氨酸拉链(GILZ),谷胱甘肽过氧化物酶3],对于其他基因,可以提供一个合理的作用机制(Claudin10,谷氨酸氨连接酶)。目前的数据可能支持使用地塞米松治疗急性感音神经性聋。在活体耳蜗中测试这些结果是有保证的。确定地塞米松在耳蜗组织中显著上调或下调其表达的基因。小鼠耳蜗组织体外培养48h后,加入或不加入地塞米松。使用涵盖33,696个转录本(24,878个基因)的微阵列和实时定量RT-PCR,比较了地塞米松处理和未处理的耳蜗组织之间的基因表达谱。微阵列分析确定了39个基因在地塞米松存在的耳蜗培养中上调或下调两倍以上。上调或下调至少三倍的基因包括FKBP5、GILZ、谷胱甘肽过氧化物酶3、Claudin 10、谷氨酸氨连接酶、蛋白多糖1、整合素类β1和糖蛋白激素的α亚基。
The microarray analysis identified 39 genes up- or down-regulated by dexamethasone in the cultured tissue of mice cochlea. Of the eight genes most highly affected, several are suggested to have protective effects in the traumatized inner ear [Fkbp5, Glucocorticoid-induced leucine zipper (Gilz), glutathione peroxidase 3] and for others, a plausible mechanism of action can be offered (Claudin10, glutamate-ammonia ligase). The present data may support the use of dexamethasone to treat acute sensorineural hearing loss. It is warrantable to test these results in the in vivo cochlea. To identify genes of which expression are markedly up- or down- regulated by dexamethasone in the cochlear tissue. Murine cochlear tissue were cultured with or without dexamethasone for 48h in vitro. The gene expression profile were compared between the dexamethasone-treated and untreated cochlear tissue using a microarray that covers 33,696 transcripts (24,878 genes) of mice and quantitative realtime RT-PCR. The microarray analysis identified 39 genes that are up- or down-regulated by more than two-fold in the presence of dexamethasone in the cochlear culture. Genes up- or down-regulated by at least threefold include Fkbp5, Gilz, glutathione peroxidase 3, claudin 10, glutamate-ammonia ligase, proteoglycan1, integrin beta-like1 and alpha subunit of glycoprotein hormone.
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发表时间: 2009-09-29
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