| Project/Area Number |
17K08680
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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 |
Pathological medical chemistry
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| Research Institution | Kindai University |
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Principal Investigator |
Man Hagiyama 近畿大学, 医学部, 助教 (60632718)
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| Project Period (FY) |
2017-04-01 – 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 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 細胞変性 / 内圧上昇 / 神経・上皮変性 / 酵素的切断 / Hippo経路 / 細胞形態 / 変性 / 細胞骨格 / 神経変性 / 接着分子 / shedding / アポトーシス |
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| Outline of Final Research Achievements |
Intraluminal pressure elevation can be pathogenic to mucosal epithelia even at a few tens cmH2O, but its effect on cell growth has not been examined intensively. A two-chamber culture system was modified to make cells receive water pressure. The cells with columnar epithelial morphology were growth-suppressed in a manner dependent on water pressure. Phalloidin staining revealed that a pressure load vertically flattened and laterally widened columnar epithelial cells and made actin fiber distribution sparse. In addition, a pressure load enhanced serine-127 phosphorylation and cytoplasmic retention of YAP, the major constituent of the Hippo pathway, suggesting that Hippo pathway was involved in the pressure-induced cell growth suppression. These results provide evidence that cell morphology and the cytoskeleton are closely linked to cell growth. Pathological intraluminal pressure elevation may cause mucosal degeneration by acting directly on this linkage and the Hippo pathway.
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| Academic Significance and Societal Importance of the Research Achievements |
内圧上昇による組織・細胞傷害は古くより知られており、その病理学的な組織所見も詳細に記述されているが、傷害発生の分子機序に関する研究は少ない。その主たる理由の1つは、発症原因となる内圧上昇が疾患や病態に関わらず非常に小さく、その軽微な加圧を可能にする培養装置が一般的には普及していないからと思われる。申請者らが考案した培養装置は、非常に安価でありながら、静的圧力の大きさを容易かつ任意に設定可能であり、速やかに普及して広く用いられるものと思われる。緑内障などの発症の分子機序解明に貢献するものと期待され、発症機序に基づく創薬シーズの探索へと発展する可能性を秘めており、社会還元の点でも意義深い。
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