| Project/Area Number |
10670012
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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 |
General anatomy (including Histology/Embryology)
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| Research Institution | Nagoya University |
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Principal Investigator |
TOIHASHI Shigeko School of Medicine, Nagoya University, Research Associate, 医学部, 助手 (90112961)
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| Co-Investigator(Kenkyū-buntansha) |
OZAKI Hiroshi The Tokyo University, Dept. of Veterinary Pharmacol., Associate Prof., 大学院・農学生命科学研究科, 助教授 (30134505)
NAKAYAMA Shinsuke School of Medicine, Nagoya University, Associate Prof., 医学部, 助教授 (30192230)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | pacemaker / c-kit / macrophages / Lipopolysaccharide / spontaneou contraction / smooth muscle / iNOS / COX-2 / c-Kit / プロスタグランジン / 単離培養 / NOS / ヒルシュスプルング病 |
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| Research Abstract |
We had inquired into two cell lines in the gastrointestinal muscle layer and obtained following results.
1. Pacemaker cells of the gastrointestinal muscle layer
Smooth muscle cells of the muscle layer have spontaneous rhythmical contractions conducted by pacemaker cells in the muscle layer. It has been realized that pacemaker cells express proto-oncogene c-kit and their development depends on c-KIT signal pathway. The present investigation realized that when c-KIT signal pathway impaired by injection of the neutralizing antibody for c-KIT into the abdomen of the newborn mouse, c-KIT positive cells failed to develop to pacemaker cells and then muscle cells disrupted spontaneous contractions. Further, c-KIT positive cells changed their developmental course, began to express smooth muscle phenotype and differentiated into longitudinal muscle cells.
2. Muscularis macrophages
Recent investigations have demonstrated that a great number of resident macrophages are located in the muscle layer and at subserosa. Electronmicroscopy revealed inactive phagocytosis under the normal condition and their functions had been unknown. Our current investigation demonstrated one of their functions, that they modulated smooth muscle contraction under pathological conditions. We measured smooth muscle contractility and studied behavior of macrophages after incubation with endotoxin lipopolysaccharide (LPS). After 4-8 hours incubation with LPS, macrophages began to express inducible enzyme cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). COX-2 produced prostaglandins (PGs) which enhanced expression of iNOS in the macrophages and promoted release of NO, which affected the mechanical activity of the muscle layer.
We focussed on two population of cell in the gastrointestinal muscle layer, i.e., pacemaker cells and muscular macrophages. We demonstrated their important roles in the muscle layer, however their interaction is the subject for a future study.
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