| Project/Area Number |
14571047
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Embryonic/Neonatal medicine
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
WADA Kazuko Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30294094)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MUSHIAKE Sohtaro Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (90291947)
KOGAKI Shigetoyo Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (00311754)
松下 享 大阪大学, 医学系研究科, 講師 (80252659)
|
|---|
| Project Period (FY) |
2002 – 2003
|
| Project Status |
Completed (Fiscal Year 2003)
|
| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2003: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
|
|---|
| Keywords | Pulmonary Fibrosis / TGF-β / LSKL / Bleomycin |
|---|
| Research Abstract |
RATIONATE TGF-β1 is a critical cytokine of fibrosis in kidney, liver and lung. Thrombospondin-1 interacts with the latency-associated peptide (LAP) in the latent TGF-β complex and regulates activation of latent TGF-β1. A peptide Leu-Ser-Lys-Leu (LSKL), which represents in the amino terminus of LAP, competitively inhibits thrombospondin-mediated activation of latent TGF-β1. We hypothesized that a peptide LSKL may reduce fibrotic change in bleomycin-treated rat lungs.
METHODS Four-week-old rats were administered LSKL or saline by nebulizer for 30 mm in chamber 2h before bleomycin (15mg/kg body weight) intratracheal injection. (LSKL group N=12, Saline group N=10). Inhalation was continued daily for 2 weeks. On 14 days, lung compliances were measured and lung tissues were used for hydroxyproline assay.
RESULTS 1) Ratio of body weight of rats at day 14 to baseline were greater in LSKIL group than in saline group (1.29±0.40 vs 1.09±0.38 p=O 44). 2) Lung compliances were significantly higher in LSKL group than in saline group (1.98±0.46 vs. 1.36±0.16 ml/cmH_2O/kg, p<O.O5). 3) The hydroxyproline content in lung tissues were significantly lower in LSKL group than in saline group (7.36±1.25 vs 9.30±1.27μg/mg lung tissue, p<O.O5).
CONCLUSION These results show that a peptide LSKL inhalation is effective to avoid deterioration of pulmonary function through prevention of progressive fibrosis in this model. Tha peptide LSKL may provide a novel therapeutic intervention in pulmonary fibrosis by blocking the activation of TGF-β1.
|
