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Differentiation of the stem cells from cochlea tissue into cochler sensory epithelial cells.

耳蜗组织干细胞分化为耳蜗感觉上皮细胞。

基本信息

批准号：
17591796
负责人：
OZEKI Masashi
金额：
$ 2.24万
依托单位：
NAGOYA CITY UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

Inhibitors of differentiation (Id) play an essential role in the neurogenesis of the central nervous system. However, the expression and function of Id in the development of cochlear sensory epithelial cells have yet to be elucidated. In this study, we demonstrate the Id1 gene was expressed in the rapidly growing otocyst on embryonic day 12 (E12) and in the organ of Corti, spiral ganglions, and stria vascularis on postnatal day 1 (P1) by cellular and molecular biologic techniques. Knockdown of the Id1 gene with short interfering RNA (siRNA) in a cochlear sensory epithelial cell line (OC1) significantly reduced its proliferation, whereas overexpression of Id1 in OC1 significantly increased the proliferation of OC1, suggesting a role of Id1 in the development of cochlear sensory epithelial cells. The proliferative action of Id1 on OC1 was mediated by nuclear factor-kappaB (NF-kappaB) and cyclin D1 (a downstream molecule of NF-kappaB). Blockage of the NF-kappaB activity with pyrrolidine dithiocarbamate (PDTC) or enhancement of the NF-kappaB activity with p65 (a subunit of NF-kappaB) in OC1 significantly inhibited or increased, respectively, the cell proliferation and transcription of cyclin D1 induced by Id1. Truncation of the NF-kappaB binding site in the cyclin D1 promoter fully abrogated the transcription of cyclin D1, suggesting that the cyclin D1 transcription is dependent on NF-kappaB. We concluded from this study that Id1 induces the proliferation of OC1 via the NF-kappaB/cyclin D1 pathway.

分化抑制剂（Inhibitors of differentiation，Id）在中枢神经系统的神经发生中起着重要作用。然而，Id在耳蜗感觉上皮细胞发育中的表达和功能尚未阐明。在这项研究中，我们证明了Id 1基因表达的快速增长的耳囊肿胚胎第12天（E12）和出生后第1天（P1）的Corti器官，螺旋神经节，血管纹。在耳蜗感觉上皮细胞系（OC 1）中用短干扰RNA（siRNA）敲低Id 1基因显著降低其增殖，而在OC 1中Id 1的过表达显著增加OC 1的增殖，表明Id 1在耳蜗感觉上皮细胞的发育中的作用。Id 1对OC 1的增殖作用是由核因子-κ B（NF-κ B）和细胞周期蛋白D1（NF-κ B的下游分子）介导的。用吡咯烷二硫代氨基甲酸酯（PDTC）阻断OC 1中NF-κ B活性或用NF-κ B亚基p65（NF-κ B的一个亚基）增强NF-κ B活性分别显著抑制或增加Id 1诱导的细胞增殖和cyclin D1的转录。在细胞周期蛋白D1启动子中的NF-κ B结合位点的截断完全废除了细胞周期蛋白D1的转录，表明细胞周期蛋白D1的转录依赖于NF-κ B。我们从这项研究中得出结论，Id 1通过NF-κ B/细胞周期蛋白D1途径诱导OC 1的增殖。