| Project/Area Number |
20590936
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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 | Hyogo College of Medicine |
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Principal Investigator |
TABATA Chiharu Hyogo College of Medicine, 医学部, 准教授 (90432393)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 非閉塞性肺疾患 / 肺線維症 / 呼吸器感染症 / その他 / サイトカイン / レチノイド / カルパイン / 悪性胸膜中皮腫 / 血管新生 / アポトーシス / サリドマイド / 放射線肺臓炎 |
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| Research Abstract |
We recently reported two substances (ATRA and thalidomide) had preventive effects on pulmonary fibrosis by inhibiting IL-6-dependent proliferation and TGF-β_1-dependent transdifferentiation of lung fibroblasts. Rheumatoid arthritis is a chronic autoimmune disorder, and its pathogenesis is also characterized by an association with several cytokines. It has been reported that Calpain, a calcium-dependent intracellular cysteine protease, plays an important role in the progression of Rheumatoid arthritis. In this study, we examined the preventive effect of Calpeptin, a calpain inhibitor, on bleomycin-induced pulmonary fibrosis.
Calpeptin histologically ameliorated bleomycin-induced pulmonary fibrosis in mice. Calpeptin decreased the expression of IL-6, TGF-β_1, angiopoietin-1, and collagen type Iα1 mRNA in mouse lung tissues. In vitro studies disclosed that Calpeptin reduced 1) production of IL-6, TGF-β_1, angiopoietin-1 and collagen synthesis from lung fibroblasts, and 2) both IL-6-dependent proliferation and angiopoietin-1-dependent migration of the cells, which could be the mechanism underlying the preventive effect of Calpeptin on pulmonary fibrosis.
These data suggest the clinical use of Calpeptin for the prevention of pulmonary fibrosis.
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