Id1 induces the proliferation of cochlear sensory epithelial cells via the nuclear factor-κB/cyclin D1 pathway in vitro
Id1 induces the proliferation of cochlear sensory epithelial cells via the nuclear factor-κB/cyclin D1 pathway in vitro
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DOI：
10.1002/jnr.21133
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发表时间：
2007-02-15
影响因子：
4.2
通讯作者：
Lin, Jizhen
中科院分区：
文献类型：
--
作者：
Ozeki, Masashi;Hamajima, Yuki;Lin, Jizhen
分化抑制因子(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过程中的表达和作用尚不清楚。在本研究中，我们用细胞和分子生物学技术证明了Id1基因在胚胎第12天(E12)快速生长的耳囊和出生后第1天(P1)的Corti器官、螺旋神经节和血管纹中都有表达。用短干扰RNA(SiRNA)敲除Id1基因可显著抑制耳蜗感觉上皮细胞系(Oc1)的增殖，而过表达Id1基因可显著促进Oc1细胞的增殖，提示Id1基因在耳蜗感觉上皮细胞的发育过程中起重要作用。Id1对OC1的促增殖作用是由核因子-kappaB(NF-kappa B)及其下游分子细胞周期蛋白D1(CyClind1)介导的。用吡咯烷二硫代氨基甲酸酯(PDTC)阻断Oc1中的NF-kappa B活性或用p65(核因子-kappaB的一个亚单位)增强其活性分别显著抑制或增强Id1诱导的细胞增殖和细胞周期蛋白D1的转录。Cyclin D1启动子中的核因子-kappaB结合位点的截断完全阻断了cyClind1的转录，提示cyClind1的转录依赖于nf-kappa B。(C)2006年Wiley-Liss，Inc.
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-kappa B (NF-kappa B) and cyclin D1 (a downstream molecule of NF-kappa B). Blockage of the NF-kappa B activity with pyrrolidine dithiocarbarnate (PDTC) or enhancement of the NF-kappa B activity with p65 (a subunit of NF-kappa B) in OC1 significantly inhibited or increased, respectively, the cell proliferation and transcription of cyclin D1 induced by Id1. Truncation of the NF-kappa B binding site in the cyclin D1 promoter fully abrogated the transcription of cyclin D1, suggesting that the cyclin D1 transcription is dependent on NF-kappa B. We concluded from this study that Id1 induces the proliferation of OC1 via the NF-kappa B/cyclin D1 pathway. (c) 2006 Wiley-Liss, Inc.