| Project/Area Number |
04670428
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Osaka University |
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Principal Investigator |
FUSAMOTO Hideyuki Osaka University Associate Prof. First Dept. of Medicine, 医学部, 助教授 (90124776)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEHARA Tetsuo Osaka University Hospital, 医学部・付属病院, 医員
ITO Toshifumi Osaka University Hospital, 医学部・付属病院, 医員
KASAHARA Akinori Osaka University Assistant Prof. First Dept. of Medicine, 医学部, 助手 (70214286)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | gastric mucosal cell / mucosal regeneration / ammonia / gastric cancer / RGM-1 / TGF-alpha / HGF / c-met / TGFα / RT-PCR / 消化管ホルモン / Epidermal Growth Factor / Hepatocyte Growth Factor / 細胞内カルシウム / ヘリコバクタピロリ / Protein kinase C |
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| Research Abstract |
1) Ammonia produced by Helicobacter pylori may play an important role in the pathogenesis of Helicobacter pylori-associated gastroduodenal discases, including peptic ulcer and gastric cancer. In this study, cytotoxicity of ammonia was investigated in rat isolated gastric mucosal cells. It was demonstrated that ammonia inhibited mitochondrial oxidative respiration, resulting in a decreased cell viability. Chronic administration of ammonia in rats produced an accelerated mucosal cell migration and an enhanced cell proliferation, leading to gastric mucosal atorophy. Further, it promoted gastric carcinogenesis induced by MHNG in rats.
2) We examined the characteristics of RGM-1, a cell line derived from normal rat gastric mucosa and established by Matsui (Riken Cell Bank) et al. RGM-1 has a polygonal shape and an immunoreactivity to cytokeration, an opithelial marker. It contains mucin granules on electron micrograph and is weakly stained by PAS staining. However, it is not stained by succinje dehydrogenase staining and Bowie's staining, and therefore js considered to be neither parictal cell nor chief cell. It grows rapidly in DMEM/F-12 medium with 20% FCS ; however, it did not form colonies in soft agar. The effects of various growth factors and cytokines on proliferation and diferrentiation of this cell line will be investigated further.
3) It is necessary to develop a new method in order to investigate expression of growth factors and their receptors during gastric mucosal regeneration in humans and experimental animals. We applied RT-PCR method to determine c-met protooncogene (HGF receptor) mRNA expression in rat gastric mucosa following mucosal injury induced by oral application of excess HC1. Expression of c-met mRNA increased in healing process of mucosal injury, suggesting that HGF and its receptor system may participate in the regeneration of the gastric mucosa.
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