L1CAM-ILK-YAP mechanotransduction drives proliferative activity of epithelial cells in middle ear cholesteatoma.
| Project/Area Number |
16K11186
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | YAP / ILK / L1CAM / middle ear cholesteatoma / メカノトランクダクション / 中耳真珠腫 / Wnt5a / 耳科学 |
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| Outline of Final Research Achievements |
Negative pressure in the middle ear is thought to be an important factor related to the etiology of middle ear cholesteatoma.
Integrin-linked kinase (ILK) interacts with extracellular matrix and results in the upregulation of mechanotransduction effector Yes-associated protein (YAP). The L1 cell adhesion molecule (L1CAM) has recently been reported as an activator of the mechanotransduction effectors related to cell proliferation and migration.
We analyzed the expression of ILK, YAP and L1CAM in stretched-middle-ear cultured cells, negative-pressure models and human cholesteatoma tissues. According to the results, the expression of cytoplasmic ILK and nuclear sift of YAP were shown to have increased in the thickened epithelium of the TM under a negative pressure load and the cholesteatoma. As results, we demonstrated the possibility that the stromal L1CAM and epithelial ILK-YAP signaling played an important role in epithelial growth under mechanotransduction in cholesteatoma formation.
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| Academic Significance and Societal Importance of the Research Achievements |
近年，細胞に加わる伸展圧迫などのメカニカルストレスは，胎児発生，加齢／老化，メタボリズム，循環器・運動器維持，腫瘍などで重要なパラメーターであることが明らかにされ，疾患解明の端緒となる新しい知見がもたらされてきている．
本研究は世界で初の中耳真珠腫発症に対するメカニカルストレスの関係を証明することができた。メカニカルストレスにより鼓膜上皮細胞に誘導されたYAP-ILKシグナル発現と上皮下間葉系細胞でのL1CAM発現により鼓膜上皮細胞増殖が活性化されることが証明できた。鼓膜上皮細胞単一異常での発症ではなく間葉系細胞との相互作用にて発症する可能性が示せ、新規保存治療開発関するに新たな知見を示せた。
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Report
(5 results)
Research Products
(16 results)
