| Project/Area Number |
09670598
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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 | Yamagata University School of Medicine |
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Principal Investigator |
KATO Shuichi Yamagata University School of Medicine.The First Department Internal Medicine., 医学部, 助手 (90260463)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Hidenori Yamagata University School of Medicine.The First Department Internal Medicine., 医学部, 講師 (30240675)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Pulmonary fibrosis / Endothelin / Gene transfer / 遺伝子導入 / 肺線維症 / 受容体アンタゴニスト |
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| Research Abstract |
Idiopathic pulmonary fibrosis (IPF) is a highly lethal disease that begins with alveolitis and irreversible interstitial fibrosis ensues. Endothelins (ET) are a family of bioactive peptides with vaso- and broncho-constrictive effects, and stimulate mitogenesis in fibroblasts. To elucidate the role of Er in the pathogenesis of pulmonary fibrosis, (1) we measured ET levels in bronchoalveolar lavage fluid (BALF) in patients with clinical signs of interstitial lung diseases (ILD). ET/albumin levels in BALF from ILD were higher than those of control subjects. There was a significant correlation between ET/albumin levels in BALF and lung functional parameters (%VC and %DLco) in ILD.(2) We assessed the effect of BQ-123, ET type A receptor antagonist, on pathologic findings in bleomycin (BLM)-induced pulmonary fibrosis in hamsters. The increased ET levels were observed in BLM-treated lungs. BLM treatment increased lung collagen levels, which was inhibited by BQ-123. Light microscopic observation of the lung revealed the amelioration of BLM-induced fibrotic changes in BQ-123 treated animals. (3) We constructed a plasmid which includes Er-1 gene driven by a cytomegalovirus promoter (pRc/CMV ET-1). Percutaneous in vivo gene transfer of pRc/CMV ET-1 with cationic liposome into the rat lung caused remarkable pulmonary fibrosis.
These findings suggest that lung ET levels play a crucial role in mediating pulmonary fibrosis.
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