| Project/Area Number |
13670609
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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 | Sapporo Medical University School of Medicine |
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Principal Investigator |
TAKAHASHI Hiroki Sapporo Medical University School of Med Associate Prof, 医学部, 助教授 (60231396)
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| Co-Investigator(Kenkyū-buntansha) |
SHIRATORI Masanori Sapporo Medical University School of Med Instructor, 医学部, 助手 (40295366)
KUORKI Yoshio Sapporo Medical University School of Med Professor, 医学部, 教授 (70161784)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | angiotensin receptor 1 / Candesartan / interstitial lung injury / lung fibrosis / type II pneumocytes / alveolar macrophage / neutrophil / 肺線維化 / Renin-Angiotensin系 / Angiotensin II receptor 1 / candesartan / 肺胞II型上皮細胞 / 急性肺傷害 / 線維化 / アンギオテンシンII / ブレオマイシン |
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| Research Abstract |
Interstitial lung diseases involve a group showing poor prognosis including idiopathic pulmonary fibrosis (IPF). A common pathophysiological change is irreversible fibrosis.
In lung tissues injured in alveolar interstitum, to make alveolar epithelial cells regenerate is very important for repair of the injured lung. Several recent studies showed that rennin-angiotensin system induces lung fibrosis and that apoptosis of type II pneumocytes is a key factor of its mechanism. However, precise manner of this system is unknown. Aims of this study were to clarify a mechanism of interstital lung injury and following fibrosis via angiotensin II receptor 1 (AT1) and to estimate an efficacy of AT1 selective antagonist (Candesartan) as a therapeutic agent against bleomycin-induced lung injury prepared in rats. Distribution of expression of AT1 receptors in normal lungs was nonspecific for many types of cells including alveolar macrophages and type II pneumocytes. Their expression in injured lungs was more extensive in neutrophils, alveolar macrophages and fibroblasts than in other types of cells. Administration of Candesartan significantly inhibited an increased content of hydroxyproline as a quantitative indicator of fibrosis, and an increased cell number of neutrophils and alveolar macrophages, whereas it did not inhibit an increased expression of AT1. Thus, this AT1 antagonist may provide an ability to modulate a process of fibrosis in the lung. A speculated mechanism by the AT1 antagonist is based on prevention of apoptosis of type II pneumocytes.
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