2005 Fiscal Year Final Research Report Summary
REGULATION OF MATRIX METALLOPROTEINASES DURING MORPHOGENESIS AND REGENERATION OF GASTROINTESTINAL EPITHELIA.
| Project/Area Number |
16590620
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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 | WAKAYAMA MEDICAL UNIVERSITY |
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Principal Investigator |
ICHINOSE Masao WAKAYAMA MEDICAL UNIVERSITY, DEPARTMENT OF GASTROENTEROLOGY, PROFESSOR, 医学部, 教授 (50143425)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Yasuhito WAKAYAMA MEDICAL UNIVERSITY, DEPARTMENT OF GASTROENTEROLOGY, ASSOCIATE PROFESSOR, 医学部, 助教授 (80235671)
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| Project Period (FY) |
2004 – 2005
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| Keywords | DEVELOPMENT / MATRIX METALLOPROTEINASE / REGENERATION / GASTROINTESTINAL TRACT / GENE EXPRESSION |
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| Research Abstract |
During the process of morphogenesis and mucosal repair in gastrointestinal tract, extensive cellular migration as well as constant remodeling of extracellular matrix (ECM) is observed. Since remodeling of ECM is regulated by ECM-degrading enzymes, matrix metalloproteinases (MMPs) could be regarded to play a pivotal role. In the present study, the roles of matrix metalloproteinase during development and regeneration of rat gastrointestinal epithelia was investigated. The profiles of MMPs activity analyzed with EITC-labeled gelatin as a substrate revealed its enhancement during the period of the stomach morphogenesis or mucosal regeneration in the gastrointestinal tract. The activity of MMP-2 was prominent in the mesenchymes during the developmental period, and the level of the active form of MMP-2 became dominant over the inactive form when the stomach underwent gland formation. MMP-2 mRNA together with that of cell surface activator of MMP-2 /membrane type matrix metalloproteinase 1 (MTl-MMP) increased during the period. MMP-9 activity was low compared with that of MMP-2, and only pro form was observed in the epithelia towards the end of fetal life. Essentially the same results was observed during stomach mucosal regeneration induced by ethanol or subserosal acetate injection. These results suggest that activities of MMPs are under a strict spatio-temporal control during stomach morphogenesis and the activity of MMP-2, which is regulated at the levels of both transcription and proteolytic activation, is deeply involved in the morphogenesis and regeneration of rat glandular stomach. Various studies using in-vitro systems also revealed that MMP-2 expression in the mesenchymal tissues is regulated by various factors regulating growth and differentiation of gastrointestinal epithelia.
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