| Project/Area Number |
11670488
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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 |
Gastroenterology
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| Research Institution | Fukui Medical University |
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Principal Investigator |
AZUMA Takeshi Fukui Medical University, Second Department of Internal Medicine, Associate Professor, 医学部, 助教授 (60221040)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Parietal cell / Acid secretion / Cell lineage / 主細胞 / ペプシノーゲンC / 胃粘膜細胞構築 |
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| Research Abstract |
The self-renewing epithelial populations present in the gastric units of the mouse stomach are descended from a multipotent stem cell and undergo an orderly migration-associated differentiation followed by apoptosis. The steady state census of the three principal cell types (acid-producing parietal cells, mucin-producing pit cells, and pepsinogen and intrinsic factor-producing zymogenic cells) is accurately controlled, despite marked differences in the rates of migration of each lineage. A transgenic mouse model has been created to define functional interrelationships between the proliferation, differentiation, and death programs of these lineages. Nucleotides -1035 to +24 of the noncatalytic β subunit gene of mouse H^+/K^+-ATPase were used to direct expression of an attenuated diphtheria toxin A subunit in the parietal cell lineage. The toxin produced complete ablation of differentiated parietal cells. Loss of parietal cells was accompanied by a 5-fold increase in the number of undifferentiated granule-free cells located in the proliferative compartment of gastruc units. Loss of mature parietal cells was also associated with a block in the differentiation of pre-neck cells and a depletion of their neck and mature zymogenic cell descendants. These results suggest that the mature parietal cell is in a strategic position to influence decision-making among gastric epithelial cell precursors and to modulate the migration-associated terminal differentiation programs of the pit and zymogenic lineages.
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