| Project/Area Number |
15590816
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Respiratory organ internal medicine
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
FUJII Takashi The University of Tokyo, The institute of Medical Science, Research Associate, 医科学研究所, 助手 (60346971)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MUKAE Hiroshi Nagasaki University School of Medicine, Second Department of Internal Medicine, Assistant Professor, 医学部・歯学部附属病院, 講師 (80253821)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
|---|
| Keywords | HSP-47 / Idiopathic Pulmonary Fibrosis / Bleomycin-induced Pulmonary Fibrosis / Collagen / Lung Fibroblast / Bronchilal epithelial cells / Antisense Therapy / 突発性肺線維症 |
|---|
| Research Abstract |
Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagen. We investigated whether treatment with the antifibrotic drug pirfenidone attenuates the bleomycin (BL)-induced overexpression of HSP47 in the lungs. Male ICR mice were intravenously injected with BL or saline (SA). Pirfenidone or control drug (CD) was administered 14 days after commencement of BL or SA, and continued throughout the course of the experiment. The mice were randomly divided into three experimental groups : 1)SA-treated with CD (SA group) ; 2)BL-treated with CD (BL group) ; and 3)BL-treated with pirfenidone (pirfenidone group). Lungs of the pirfenidone group showed a marked reduction of fibrotic lesions compared with the corresponding BL group. Immunohistochemical studies showed that BL treatment significantly increased the number of macrophages, myofibroblasts, HSP47-positive type II pneumocytes and HSP47-positive interstitial spindle-shaped cells. Treatment with pirfenidone significantly reduced the number of these cells compared with the corresponding BL group. Furthermore, treatment with pirfenidone significantly suppressed the BL-induced increase of the positive ratio of HSP47 and alpha-smooth muscle actin to interstitial spindle-shaped cells. This study results showed that pirfenidone inhibited heat shock protein 47-positive cells and myofibroblasts, the principal cells responsible for the accumulation and deposition of extracellular matrix seen in pulmonary fibrosis.
|
