1999 Fiscal Year Final Research Report Summary
Regulation of Apoptosis in the epithelia of rat gastrointestinal tract
| Project/Area Number |
10670453
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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 | The University of Tokyo |
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Principal Investigator |
ICHINOSE Masao The University of Tokyo, The Department of Internal Medicine, Lecturer, 医学部・附属病院, 講師 (50143425)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Apoptosis / Gastrointestinal epithelium / Anoikis |
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| Research Abstract |
1) Using the primary culture of rut gastrointestinal epithelia, we have investigated the apoptosis in these tissues. Among the gastrointestinal epithelia, that of the stomach is most resistant to apoptosis induced by TGF-β family! The inducibility of apoptosis by the growth factors becomes more potent as the developmental stage advances in the gastrointestinal tract. The induction of the apoptosis was suppressed dose-dependently by HGF or EGF.
2) In the gastrointestinal tact anoikis starts from both glandular tip or surface cells of the epithelia and extended to include the whole gland in a relatively short time. The stomach epithelia is more resistant to the process of anoikis than that of any other region. The process of anoikis was markedly enhanced by the treatment of hydrocortisone or NSAIDS.
3) The process of apoptosis induced by TGF-β, and also anoikis was inhibited in a dose-response manner by an inhibitor of tyrosine-phosphorylation, sodium orthovanadate. We are now analyzing the tyrosine-phosphorylation of Focal adhesion kinase (FAK) and other protein substrate, and also trying to identify the species of caspase activated during the process of apoptosis.
4) The effects of the initiators and promotes of stomach carcinogenesis on apotosis of stomach epithelia was investigated. Rats were treated with MNNG or NaCl, and only those indicating altered histology specific for the stomach carcinogenesis was used for the analyses. No evidence of the altention in the process of apoptosis was obtained.
In conclusion, the results of the present studies revealed the processes of apoptosis of the gastrointestinal epithelia is regulated region- and developmental stage-specific manners by both various soluble growth factors and insoluble components of extracellular matrix. The involvement of the regulatory mechanism utilizing of protein phosphorylation of FAK and other protein substrate was suggested ht the process of apoptosis in the gaastrointestinal epithelia.
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[Publications] Matsubara Y, Ichinose, Yahagi N, Tsukada S, Oka M, Miki K, Kimura S, Omata M, Shiokawa K, Kitamura N, Kaneko Y and Fukamachi H: "Hepatocyte growth factor activator : A possible regulator of morphogenesis during fetal development of the rat gastrointestinal tract."Biochemical and Biophysical Research Communications. 253. 477-484 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Matsushima M, Ichinose M, Yahagi N, Tsukada-Kato S, Miki K, Omata M, Kim Y, Ito H, Takahashi T, Sakurai Y, Athauda SBP, Inoue H and Takahashi K: "Purification and further characterization of enteropeptidase from porcine duodenum."Journal of Biochemistry. 125. 947-951 (1999)
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[Publications] Ichinose M, Yahagi N, Matsubara M, Kato S, Oka M, Kido M, Tsuji M, Shimizu Y, Omata M, Kimura S, Miki K and Fukamachi H: "The method for isolation of gastrointestinal epithelial cells and primary serum-free culture of pyloric gland epithelia from adult rat (in Japanese)."Terapeutic Research. 20. 161-167 (1999)
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