Analysis of tissue degeneration by internal pressure elevation
Project/Area Number |
18K07049
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 49030:Experimental pathology-related
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Research Institution | Kindai University |
Principal Investigator |
Ito Akihiko 近畿大学, 医学部, 教授 (80273647)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | 変性 / 内圧上昇 / 接着分子 / 蛋白凝集 / 異性体化 / 神経変性 / 緑内障 / 光学異性体 / アスパラギン酸 / D体化 / D体化アスパラギン酸 / 組織変性 / 病的内圧 / 異性体転換 |
Outline of Final Research Achievements |
Various epithelial and neuronal cell lines were cultured in the system where cells were loaded with static water pressure comparable with pathogenic elevation of internal pressure, and were examined for changes in cell growth, cell shape, cytoskeletons, and expression of inter-cellular adhesion molecule CADM1. When loaded with pressure, epithelial cells became flat and large in volume, and their doubling time increased. In neuronal cells, CADM1 ectodomain shedding increased, the resulting intracytoplasmic fragment aggregated, and neurite degeneration occurred. The C-terminal portion of this fragment (25-amino acid-long peptide) was synthesized. When this peptide was left in saline, it got D-isomerization in the asparagine residue (LC-MS analysis). This D-isomerization may be one of the causes of peptide aggregation in neurites.
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Academic Significance and Societal Importance of the Research Achievements |
内圧上昇により種々の変性病変が生じるが、その機序は未解明であり、また、根本的な治療法もない。本研究の成果として、内圧上昇の結果、上皮細胞には有意な形態の変化が惹起されるとともに、細胞の増殖も抑制されることが見出された。一方、神経細胞においては、細胞内に蛋白凝集が生じることが明らかとなり、その機序としてアスパラギン酸異性体化(D体化)の関与が示唆された。 内圧上昇と密接に関連する代表的な疾患としては緑内障、水頭症、水腎症などが挙げられる。これらの疾患における変性病態を理解する上で、重要な知見が得られたと考えられる。
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Report
(4 results)
Research Products
(40 results)
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[Journal Article] Ectopic TWEAKR expression in type I fiber of stroke-prone spontaneously hypertensive rats is related to slow muscle-specific hypotrophy.2019
Author(s)
Inoue T, Hagiyama M, Maenishi O, Kimura M, Mizuguchi N, Mine Y, Kimura R, Chikugo T, Itoh T, Satou T, Ito A
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Journal Title
Life Sciences
Volume: 237
Pages: 116919-116919
DOI
Related Report
Peer Reviewed
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[Journal Article] A comparative study of curated contents by knowledge-based curation system in cancer clinical sequencing.2019
Author(s)
Sakai K, Takeda M, Shimizu S, Takahama T, Yoshida T, Watanabe S, Iwasa T, Yonesaka K, Suzuki S, Hayashi H, Kawakami H, Nonagase Y, Tanaka K, Tsurutani J, Saigoh K, Ito A, Mitsudomi T, Nakagawa K, Nishio K
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Journal Title
Scientific Reports
Volume: 9
Issue: 1
Pages: 11340-11340
DOI
Related Report
Peer Reviewed
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[Journal Article] Clinical and immune profiling for cancer of unknown primary site.2019
Author(s)
Haratani K, Hayashi H, Takahama T, Nakamura Y, Tomida S, Yoshida T, Chiba Y, Sawada T, Sakai K, Fujita Y, Togashi Y, Tanizaki J, Kawakami H, Ito A, Nishio K, Nakagawa K
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Journal Title
Journal for immunotherapy of cancer
Volume: 7
Issue: 1
Pages: 251-251
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Urinary cell adhesion molecule 1 is a novel biomarker that links tubulointerstitial damage to glomerular filtration rates in chronic kidney disease.2019
Author(s)
Hagiyama M, Nakatani Y, Takashima Y, Kato T, Inoue T, Kimura R, Otani T, Sato Y, Mori H, Arima S, Ito A
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Journal Title
Frontiers in Cell and Development Biology
Volume: 7
Pages: 111-111
DOI
Related Report
Peer Reviewed / Open Access
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