2001 Fiscal Year Final Research Report Summary
anti-apoptotic signaling pathway in gastric mucous cells
| Project/Area Number |
12670480
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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 | KYOTO UNIVERSITY |
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Principal Investigator |
KONDA Yoshitaka Kyoto University Graduate School of Medicine, Gastroenterology and hepatology, assistant professor, 医学研究科, 助手 (90261867)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Gastric pit cells / TGF α / apoptosis / NF-κB |
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| Research Abstract |
Background ＆ Aims : Recently, some growth factors have been shown to play roles not only as a growth factor but also as a cell surviving factor. Transforming growth factor-α (TGF-α) is expressed in normal gastric mucosa. In this study, we investigated the cell surviving effect of TGF-α on gastric mucosal cells as well as its signaling mechanism. Methods : We used gastric mucosal cell line, GSM06 and gastric cancer cell line, AGS. Apoptosis was induced by serum depletion or exposure to sodium butyrate. Analysis of apoptosis was performed by DNA ladder assay, measuring DNA fragmentation ratio (Burton method), and DAPI staining. Results : We found that pit cells migrating outward expressed both TGF-α and epidermal growth factor receptor (EGF-R) in rat oxyntic glands, but the cells at the top of the gland, which showed on-going apoptosis by TUNEL staining, did not express either of them, suggesting protective effect of TGF-α on pit cells from apoptosis in vivo. TGF-α protected gastric mucosal cells against apoptosis induced by serum depletion or sodium butyrate in a dose dependent manner. This anti-apoptotic effect of TGF-α was blocked by the pretreatment with NF-κB inhibitors, whereas neither MEK inhibitor PD098059 nor PI-3-kinase inhibitor wortmannin abolished this effect. Electrophoretic mobility shift assay (EMSA) showed NF-κB activation by TGF-α stimulation. TGF-α also enhanced the expression of Bcl-2 family proteins in NF-κB-dependent manner. Conclusions : TGF-α plays an anti-apoptotic role in gastric mucosal cells via NF-κB dependent pathway.
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Research Products
(8 results)
