2002 Fiscal Year Final Research Report Summary
Expression of highly differentiated functions in gastric mucosal cells by paracrine mechanisms between distinct cell-types and appearance of adherent property to H. pylori in inverse proportion to decline in their differentiated functions
| Project/Area Number |
12470118
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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 |
Gastroenterology
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| Research Institution | Gunma University |
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Principal Investigator |
TAKEUCHI Toshiyuki Gunma University, Department of Molecular Medicine, Institute for Molecular and Cellular Regulation, Professor, 生体調節研究所, 教授 (00109977)
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| Co-Investigator(Kenkyū-buntansha) |
SUGANO Kentaro Jichi Medical School, Department of gastroenterology and hepatology, Professor, 医学部, 教授 (60179116)
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| Project Period (FY) |
2000 – 2002
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| Keywords | Gastrin / Gastrin receptor / CCK-B / Furin / TGFβ / Gastric surface mucous (GSM) cells / Chief cells / Calpain / Calpastatin |
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| Research Abstract |
The gastric gland is consists of at least 11 distinct cell-types, including gastric surface mucous (GSM) cells (=pit cells), parietal cells, chief cells, and enterochromaffin-like (ECL) cells. Their differentiation is regulated by a variety of growth factors including TGFa and TGFb, gastrin, and cell-to-cell or cell-to-matrix interaction signals. With the four studies below, we showed evidence that expression of highly differentiated gastric functions requires formation of functional localization of each cell-type.
(1) Gastrin/CCK-B receptors (CCKB-Rs) are present on parietal and ECL cells, but not on pit cells. However, serum gastrin levels are well correlated with the growth of the gastric pit. In situ hybridization indicated that CGKB-R mRNA was faintly distributed along the mid-to low-glandular region in the hypergastrinemic transgenic mouse mucosa. Thus, gastrin directly stimulates the growth of the pit cells.
(2) Furin, a proprotein-convertase, is distributed in the upper third lay
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er and the lower quarter region of the gastric gland. We identified the upper furin-positive cells as parietal cells and the lower cells as chief cells. Chief cells express three isoforms of TGFb, which requires cleavage by furin for its activation. TGFa induced an increase in the expression of furin and TGFb mRNAs in primary-cultured chief cells.
(3) TGFa is highly expressed in the pit cells. TGFa protected GSM cells against apoptosis and enhanced the expression of Bcl-2. This antiapoptotic effect is mediated by the NF-kB-dependent pathway.
(4) Calpain is a calcium-activated protease. We found four calpain isoforms and calpain inhibitor calpastatin localized in distinct cell-types of the gastric mucosa. Calpastatin significantly blocks cell migratory capacity.
Although we could not show the appearance of strong adherent property of gastric membranes to H. pylori by the decline of glandular structure, we provided substantial understandings to complicated glandular structures which are vulnerable to H. pylori invasion. Less
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