| Project/Area Number |
03670536
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Dermatology
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
TAKADA Koji Kawasaki Med.Sch., Faculty of Medicine, Assistant Prof, 医学部, 講師 (20163404)
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| Co-Investigator(Kenkyū-buntansha) |
MORI Kenichi Kawasaki Med.Sch., Faculty of Medicine, Assistant, 医学部, 助手 (50248225)
HAMASAKI Yoichiro Kawasaki Med.Sch., Faculty of Medicine, Assistant Professor, 医学部, 講師 (10180936)
UEKI Hiroaki Kawasaki Med.Sch., Faculty of Medicine, Professor, 医学部, 教授 (30069017)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1991: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | connective tissue metabolism / I, III, VI collagen / Collagenase / Gene expression / Scleroderma / Tumor necrosis factor / Cyclosporin A / Skin fibroblasts / コラーゲン代謝 / VI型コラーゲン / ウェルナー症候群 / 全身性強皮症 / コラ-ゲン代謝 / I,III型コラ-ゲン / コラゲナ-ゼ / モルフェア / 先天性皮膚弛緩症 / ヒスタミン / シクロスポリンA |
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| Research Abstract |
To understand the modulation of collagen metabolism and collagen gene expression in physiological and pathological conditions of connective tissue, we investigated whether histamine, cyclosporin A, pentoxifylline and tumor necrosis factor alpha (TNF alpha) affect collagen synthesis and collagen degradation in cultured skin fibroblasts. Histamine (1-10 mug/ml) stimulated collagen synthesis at the pretranslational level, however cyclosporin A (10^<-8>-10^<-6>M) did not affect to collagen expression at the therapeutic concentrations. The mRNA levels of alpha_1(I) collagen and fibronectin were decreased in pentoxifylline-treated (10-100 mug/ml) fibroblasts. TNF inhibited collagen synthesis and collagen I, III, and fibronectin mRNA levels, and stimulated collagenase expression in normal and scleroderma fibroblasts, while collagen VI mRNA levels were unaltered. We also found that collagen VI expression in Werner's syndrome fibroblasts, which has indicated that increased collagen synthesis ac
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companies increased collagen I and III mRNA, were decreased. These results showed that collagen VI expression was regulated independently from that of collagen I and III in fibroblasts. Cutis laxa (CL) is suggested that there are abnormalities in the elastic fiber of connective tissue. We found that increased collagenase activity and collagenase mRNA level were detected in CL fibroblasts. It was suggested that increased collagenase expression of fibroblasts was related to connective tissue abnormality in CL. Finally, collagen metabolism in scleroderma fibroblasts were studied. In localized scleroderma, collagen gene expression in fibroblasts from inflammatory lesions were increased, whereas fibroblasts from sclerotic lesions were unaltered. In systemic sclerosis (SSc), collagen gene expression in cultured fibroblasts were increased in only two of eight strains. On the other hand, collagenase activity and its production were decreased in all SSc fibroblasts. However, no alterations were detected in collagenase mRNA levels. These results suggest that one of mechanisms of collagen deposition in SSc might be caused by decreased collagenase production at the translational or post-translational levels. Less
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