| Project/Area Number |
16590736
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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 |
Respiratory organ internal medicine
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| Research Institution | Chiba University |
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Principal Investigator |
KASAHARA Yasunori Chiba University, Graduate School of Medicine, Instructor, 大学院・医学研究院, 助手 (60343092)
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| Co-Investigator(Kenkyū-buntansha) |
TATSUMI Koichiro Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (10207061)
KURIYAMA Takayuki Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (20009723)
SEKI Naohiko Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (50345013)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | COPD / Emphysema / VEGF / Smoking / Endothelial Progenitor Cells / Bone Marrow / Mouse |
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| Research Abstract |
Introduction : We have postulated that cigarette smoking induced COPD may occur due to a failure of the cellular and molecular maintenance program of the lung. Previous reports have suggested that bone marrow progenitors plays important roles in pulmonary regeneration and maintenance. We hypothesize that cigarette smoking may contribute the level of vascular endothelial growth factor (VEGF) and bone marrow derived stem cells in emphysema.
Methodology : C57BL/6J (B6) male mice were exposed to 20 cigarettes for 60 min per day for either 1 day (acute phase), 1 week (subacute), 4 weeks (chronic), or 6 months (chronic). Age-matched B6 mice were used as controls. Mononuclear cells were isolated from bone marrow and peripheral blood cells by density gradient centrifugation. We quantified the number of VEGFR-2/Sca-1(Stem cell antigen-1) double positive cells using 2-color flow cytometric analyses.
Results : The mean linear intercept, as a measure of interalveolar wall distance, was significantly greater in smoking mice lungs when compared with control mice lungs. An increased production of VEGF in the lung extracts was seen in the subacute phase. VEGF in the lung extracts decreased significantly in the chronic phases. The number of alveolar macrophages in the chronic smoking-exposed lungs was increased in the subacute phase, with subsequent decreases in the chronic phases, but was still higher than that of control mice during both phases. VEGFR-2/Sca-1 double positive cells in the peripheral blood of smoking mice were not significantly differed in the chronic smoking. However, the smoking mouse had significantly increased the number of EPCs in the bone marrow in the subacute smoking.
Conclusion : These data suggest the existence of a smoking duration-dependent modulation of VEGF production in the lung upon cigarettes smoking. bone marrow derived stem cells may be important role in the pathogenesis of emphysema.
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