| Project/Area Number |
17591796
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | NAGOYA CITY UNIVERSITY |
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Principal Investigator |
OZEKI Masashi Nagoya City University, Graduate School of Medical Sciences, Research Fellow, 大学院医学研究科, 研究員 (80315887)
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| Co-Investigator(Kenkyū-buntansha) |
HIDA Hideki Nagoya City University, Graduate School of Medical Sciences, Associate, 大学院医学研究科, 助教授 (00305525)
HAMAJIMA Yuki Nagoya City University, Graduate School of Medical Sciences, Research Associate, 大学院医学研究科, 助手 (30343403)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | ID1(inhibitor of differentiation1) / NF-kappaB / cyclin D1 / cochlear sensory epithelial cells / 内耳多能幹細胞 / セルライン / Notch,HES1,math1,Wnt遺伝子 / 内耳有毛細胞の分化 |
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| Research Abstract |
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.
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