2000 Fiscal Year Final Research Report Summary
Development of novel therapeutics targeting the function of intestinal cells of Cajal in gastrointestinal motility disorder
| Project/Area Number |
11557042
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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 | 展開研究 |
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| Research Field |
Gastroenterology
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| Research Institution | Osaka University |
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Principal Investigator |
SHINOMURA Yasuhisa Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90162619)
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| Co-Investigator(Kenkyū-buntansha) |
MURAYAMA Yoko Osaka University Hospital, Medical Staff, 医学部・附属病院, 医員
KIYOHARA Tatsuya Osaka Unversity Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (50322178)
MIYAZAKI Yoshiji Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30303960)
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| Project Period (FY) |
1999 – 2000
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| Keywords | gastrointestinal motility / interstitial cells of Cajal / pacemaker / c-kit |
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| Research Abstract |
Interstitial cells of Cajal (ICCs) are found as networks of cells associated with neuronal plexuses in gastrointestinal tract. Recent studies have provided evidence that ICCs function in the gut as pacemaker cells responsible for the generation of spontaneous electrical activity. We have shown the deficiency of ICCs and the decrease in the contractile activity of the intestine in spontaneous mutant rats with a small deletion at the tyrosine kinase domain of c-kit. We have also shown the deficiency of ICCs in patients with a myopathic form of chronic intestinal pseudo-obstruction. Most types of chronic intestinal pseudo-obstruction do not respond to conventional prokinetic drugs. Therefore, methods of novel therapeutics need to be developed by targeting the molecules associated with the regulation of proliferation, differentiation and function of ICCs. We are investigating the mechanism of the regulation of proliferation, differentiation and function of ICCs. We have established in vitro culture system for ICCs isolated from mouse intestine and intestinal stromal cell line. Stem cell factor (SCF), which is a ligand of c-kit, stimulated the proliferation of ICCs from day-8 postcoitus embryos. SCF did not stimulate the proliferation of ICCs from day-6 postpartum neonates but SCF was needed for their survival. We have developed stromal cell lines originating from the small intestine of the mouse. The stromal cells transfected with c-kit complementary DNA showed the tendency to differentiate to ICCs. We are going to identify the molecules that can be targeted to induce differentiation.
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[Publications] N.Sawada-Hase, T.Kiyohara, J.Miyagawa, H.Ueyama, K.Isozaki, Y.Murayama, T.Kashihara, M.Nakahara, R.Nezu, Y.Shinomura, Y.Matsuzawa: "Enhanced CD40 expression and high IL-12 production by intestinal macrophages and peripheral blood monocytes in patients with Crohn's disease."Am.J.Gastroenterol. 95(6). 1516-1523 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] S.Kitamura, S.Kondo, Y.Shinomura, K.Isozaki, S.Kanayama, Y.Higashimoto, T.Minami, T.Kiyohara, Y.Yasunaga, H.Ishikawa, T.Ohtani, S.Ishiguro, Y.Matsuzawa: "Expression of hepatocyte growth factor and c-met in ulcerative colitis."Inflamm.Res.. 49(7). 320-324 (2000)
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「研究成果報告書概要(欧文)」より
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