Choromatin modifier-associated cellular differentiation of pulmonary epithelial cells to neuroendocrine cells
| Project/Area Number |
16590764
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Tokyo University of Pharmacy and Life Sciences |
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Principal Investigator |
TAKAHASHI Yuji Tokyo University of Pharmacy and Life Sciences, School of Life Science, Professor, 生命科学部, 教授 (20154875)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Shigeru Tokyo University of Pharmacy and Life Sciences, School of Life Science, Associate Professor, 生命科学部, 助教授 (10266900)
HIROSE Hidenori Tokyo University of Pharmacy and Life Sciences, School of Life Science, Research Associate, 生命科学部, 助手 (80398817)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | lung epithelium / neuroendocrine cell / cell differentiation / lung damage / hypoxia / ATF5 / Notch / Shh / 神経内分泌細胞 / 転写調節因子 / Neuroendocrine / 肺発達 / 低酸素刺激 / Mash1 / Hes1 |
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| Research Abstract |
Lung epithelial neuroendocrine cells are defferenciated from multipotent stem cell in lung at the mid term of the pregnancy in human. Pulmonary neuroendocrine cells secret catecholamine and neural peptides, resulting in the regulation of the proliferation and differentiation of lung epithelial cells. It could be possible that neuroendocrine cell differentiation may be associate to pathogenesis of lung diseases. We hypothesized that chromatin-modifier might modulate the differentiation of neuroendocrine cell. To understand the mechanism of pulmonary neuroendocrine cell, we established the in virto cell culture system in which multi-potent stem cell of lung epithelium can differentiate to neuroendocrine-like cells. Interaction collagen matrix and hypoxic condition are important conditions that differentiate the premature pulmonary epithelial cells to neuroendocrine cells. Gene expression profiles under cell differentiation indicated that biphasic up-regulation of Ash1 and ATF5 might be critical for the determination of the epithelial cells for the neuroendocrine differentiation. In these processes, ATF5 associated chromatin modifier and regulated the target genes. To assess the role of ATF5 in this process, we tried to produce monoclonal antibody against ATF5. Several clones showed the specific binding to ATF5 protein. But we could not detect ATF5 protein in the normal lung. This suggested that half life of ATF5 protein in the cell might be very short. Our research, now, is ongoing to identify the mechanism of protein stabilization and its association to the pulmonary neuroendocrine cell differentiation.
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Report
(3 results)
Research Products
(1 results)
