| Project/Area Number |
11470143
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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 | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Nippon Medical School |
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Principal Investigator |
KAWANAMI Oichi Nippon Medical School, Institute of Gerontology, Professor, 老人病研究所, 教授 (70096973)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIWARA Masakazu Nippon Medical School, Institute of Gerontology, Lecturer, 老人病研究所, 助手 (20312069)
JIN Enjing Nippon Medical School, Institute of Gerontology, Lecturer, 老人病研究所, 助手 (10312068)
GHAZIZADEH Mohammad Nippon Medical School, Institute of Gerontology, Associate Professor, 老人病研究所, 助教授 (30190979)
EMI Mitsuru Nippon Medical School, Institute of Gerontology, Professor, 老人病研究所, 教授 (90221118)
OHTA Shigeo Nippon Medical School, Institute of Gerontology, Professor, 老人病研究所, 教授 (00125832)
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| Project Period (FY) |
1999 – 2001
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| Keywords | alveolar capillary / vascular endothelial cell / protease-activated receptor / thrombomodulin / thrombin / lung adenocarcinoma / lung injury / serine protease |
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| Research Abstract |
Morphology of the alveolar capillaries in the lung has been well documented under healthy and pathologic conditions. However, so-far available results could be summarized as plain observations by light and electron microscopies, and the functional implication derived from them is far from satisfactory. In order to explain and evaluate phenotypic activation of alveolar capillary endothelial cells, our observation has been focusing on a single unit capillary of alveolar walls in the lung. Together with electron and confocal laser scanning microscopies, multiple probing antigens, including anticoagulant thrombomodulin (TM), coagulant von Willebrand factor (vWf), protease-activated receptors (PAR) and their ligand-serine proteases, have been applied on human and experimental animal lungs. Important and novel findings we have obtained were as follows : 1) alveolar capillary endothelium lacked a conventional expression of vWf, but fully covered by TM ; 2) immunohistochemical conversion, from TM- to vWf-dominant phenotype, underwent when alveolar walls were damaged or metastasized by neoplastic cells of primary lung adenocarcinoma ; 3) PAR in endothelial cells elicited by nearby neoplastic cells facilitated a loss of TM while vWf started to accumulate ; and 4) activation of PAR on endothelial cells by serine proteases such as thrombin lead to exert a variety of biological activities, including cell growth and collagen production in alveolar wall cells. Thus, alveolar capillary endothelial cells might at least partly be a primary stimulator for repairing alveolar damages. In this connection alveolar capillary endothelial cells would be deeply involved in promoting cellular network functions among the alveolar wall cells. Our research aims are forwarding further to evaluate basic functions of endothelial cells in collagen vascular disease-related lung fibrosis.
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