The development of basic technologies for the cellular therapy of corneal epithelial cells by the regulation of cellular senescence and epigenetic changes
| Project/Area Number |
20390451
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
KINOSHITA Shigeru Kyoto Prefectural University of Medicine, 医学研究科, 教授 (30116024)
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| Co-Investigator(Kenkyū-buntansha) |
KAWASAKI Satoshi 京都府立医科大学, 医学研究科, 助教 (60347458)
INATOMI Tsutomu 京都府立医科大学, 医学研究科, 助教 (00305583)
MATSUDA Akira 順天堂大学, 医学部, 准教授 (00312348)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000)
Fiscal Year 2010: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2009: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2008: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
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| Keywords | 細胞老化 / エピジェネティクス / 角膜上皮 / 眼表面疾患 / 移植再生医療 / 移植再生治療 / エピジェネティックス / 遺伝子導入 / プラスミド / レンチウイルス |
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| Research Abstract |
In this study, in order to establish the method to transplant corneal epithelial cells which are amplified ex vivo from the limited number of autologous corneal epithelial cells, we investigated the cellular senescence and epigenetic changes of the cultured corneal epithelial cells as well as the possible countermeasures against these culture-associated drawbacks. We have found that the expression of the keratin 12 gene significantly decreased rapidly after the cell dissociation of the corneal epithelial cells, which was found to be due to the activation of several signaling pathways such as MAPK accompanied with the epigenetic changes of the keratin 12 promoter. The proliferation of the corneal epithelial cell was found to be significantly enhanced by the introduction of SV40 large T antigen which is known to inhibit p53 and Rb tumor- suppressive pathways. Quite interestingly, when corneal epithelial stem cells were transfected with the SV40 large T antigen, the endogenous hTERT gene was found to be activated, which is thought to be the risk to lead the tumorigenic transformation of these cells.
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Report
(4 results)
Research Products
(29 results)
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[Journal Article] Three susceptible loci associated with primary open-angle glaucoma identified by genome-wide association study in a Japanese population.2009
Author(s)
Nakano M, Ikeda Y, Taniguchi T, Yagi T, Fuwa M, Omi N, Tokuda Y, Tanaka M, Yoshii K, Kageyama M, Naruse S, Matsuda A, Mori K, Kinoshita S, Tashiro K.
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Journal Title
Proc Natl Acad Sci U S A. 106
Pages: 12838-12842
Related Report
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