Project/Area Number |
10671680
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Plastic surgery
|
Research Institution | KAGAWA MEDICAL UNIVERSITY |
Principal Investigator |
KOBAYASHI Ryoji (1999) Kagawa Medical University, Faculty of Medicine, Professor, 医学部, 教授 (00020917)
獅々堀 彊 (1998) 香川医科大学, 医学部, 助教授 (10033870)
|
Co-Investigator(Kenkyū-buntansha) |
SHISHIBORI Tsuyoshi Kagawa Medical College, Professor, 臨床検査学科, 教授 (10033870)
HATA Yuiro Kagawa Medical University, Faculty of Medicine, Professor (90164839)
小林 良二 香川医科大学, 医学部, 教授 (00020917)
|
Project Period (FY) |
1998 – 1999
|
Project Status |
Completed (Fiscal Year 1999)
|
Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥2,700,000 (Direct Cost: ¥2,700,000)
|
Keywords | extracellular matrix protein / elastin / 36-kDa MAGP / microfibril / tranilast / molecular pharmacology / drug affinity chromatography / 36kDaMAGP / エラスチン繊維 / 細胞接着 / Smith-Magenis症候群 / ミクロフィブリル / 細胞外マトリックス蛋白質 / RGD蛋白質 / アフィニティクロマトグラフィー |
Research Abstract |
To elucidate the molecular mechanism involved in the suppression of keloids and hypertrophic scars by tranilast, we investegated the target proteins of tranilast and other anti-allergic drugs in bovine skin and aorta. A specific tranilast-binding protein was isolated from both tissues by drug affinity chromatography and was identified as 36-kDa microfibril-associated glycoprotein (36-kDa MAGP). Binding of 36-kDa MAGP to tranilast seemed to be specific since 36-kDa MAGP could be eluted from the drug affinity column by tranilast itself and also binding of 36-kDa MAGP to other anti-allergic drugs, such as cromolyn and amlexanox, is significantly weaker than that to tranilast. Light and electron microscopic immunohistochemistry detected the protein at the periphery of elastic fibers in normal human skin. In hypertrophic scar tissue, however, 36-kDa MAGP was located on small bundles of microfibrils. These findings provide support for te concept that elastogenesis occurs in scar tissue and 36-kDa MAGP might be one of the target for tranilast. Based on the evidence, we synthesized several compounds which specifically bind to 36-kDa MAGP.
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