| Project/Area Number |
13670867
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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 |
Dermatology
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| Research Institution | CHIBA UNIVERSITY |
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Principal Investigator |
SHINKAI Hiroshi Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (90030957)
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| Co-Investigator(Kenkyū-buntansha) |
ENDO Hideharu Chiba University, Graduate School of Medicine, Assistant, 大学院・医学研究院, 助手 (50282489)
UTANI Atsushi Chiba University, University Hospital, Lecturer, 医学部附属病院, 講師 (10292707)
HATAMOCHI Atsushi Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (90172923)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | Ehlers-Danlos / Decorin / SLRP / Dermatopontin / gene targeting / collagen fibril / Wound healing / 強皮症 |
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| Research Abstract |
Gene targeting of a member of small leucine-rich repeat proteoglycans demonstrates that collagen fibrillogenesis is mediated by a set of extracellular matrix components, which interact with collagen. Collagen-associated protein dermatopontin knockout mice were generated in order to analyze the biologic involvement of dermatopontin in the formation of collagen fibrils. Although dermatopontin-null mice did not exhibit any obvious anatomical abnormality, skin elasticity was increased. Skin tensile tests revealed that the initial elastic modulus was 57% lower in dermatopontin-null mice than in wild-type mice, and that maximum tensile strength was similar. Remarkably, light microscopy study showed a significant decrease in the relative thickness of the dermis in dermatopontin-null mice compared with wild-type mice (45.2 +/- 3.09% and 57.8 +/- 4.25%, respectively,). The skin collagen content was 40% lower in dermatopontin-null than in wild-type mice. Collagen fibrils in dermatopontin-null mi
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ce showed a great variety in diameter and irregular contours under the electron microscope.
A comparison of wound healing was developed by excision of 4mm diameter full thickness skin in dermatopontin null mice and wild type mice. The results indicated that wound re-epithelialization in those animal showed no difference between wild- type mice. Analysis of gene expression of SLRPs and fibromodulin was assessed by use in sitsu hybridization. The results indicate that mRMA of dermatopontin paralleled each other throughout the healing process in wild type mice. Electron microscopic examination showed the presence of larger collagen fibrils in diameter in dermatopontin null mice of upper dermis compared with those of wild type mice. A great variety in diameter and irregular collagen fibrils distribute in deep dermis in dermatopontin-null mice.
These data indicate that dermatopontin plays a critical role in elasticity of skin and collagen accumulation attributed to collagen fibrillogenesis in vivo. Less
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