| Project/Area Number |
16K20221
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 後天性中耳真珠腫 / Notchシグナル / 後天性真珠腫 / 耳科学 |
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| Outline of Final Research Achievements |
We analyzed gene expression related to Notch signaling of acquired middle ear cholesteatoma using PCR array kit. As a result, the expression of NOTCH1 in middle ear cholesteatoma epithelium significantly decreased than that in normal external ear canal epithelium, and the expression of HES1, which is a target gene of NOTCH1, tended to decrease. The study using Hes1 KO mice have revealed that notch signaling promoted spinous cell fate specification from basal layer cells and further induced granular differentiation, but simultaneously prevented further differentiation to maintain an immature spinous fate in a Hes1-dependent manner. The expression change of HES1 through notch signaling may play an important role in the pathophysiology of middle ear cholesteatoma.
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| Academic Significance and Societal Importance of the Research Achievements |
後天性中耳真珠腫における角化扁平上皮の異常増殖性に関して、Notchシグナルを介したHES1の発現変化が病態生理に関与している可能性が本研究にて明らかになった。このことから、Notchシグナル関連分子の中から後天性中耳真珠腫に対する新たな治療標的因子が見つかる可能性がある。後天性真珠腫の発症原因は未だ明確にされておらず、依然として根本的治療は外科的治療のみであるが、新たな標的分子、シグナル伝達機構を解明することができれば、今後の後天性真珠腫治療におけるbreak throughとなり、真珠腫の非外科的治療法開発へ大きな一歩となることが期待される。
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