| Project/Area Number |
11470371
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Plastic surgery
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
MINAKAWA Hidchiko Hokkaido Univ., Grad.school of Med., Asso.Prof, 大学院・医学研究科, 助教授 (80229757)
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| Co-Investigator(Kenkyū-buntansha) |
KUZUMAKI Noboru Hokkaido Univ., Institute for Genetic Medicine., Prof., 遺伝子病制御研究所, 教授 (80091445)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2000: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1999: ¥7,300,000 (Direct Cost: ¥7,300,000)
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| Keywords | keloid / fibroblast / intracellular signal transduction / apoptosis / molecular biology / MAPK |
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| Research Abstract |
1. After stimulation with growth factors, we studied the phosphorylation of ERK, JNK, and p38 in keloid-derived fibroblasts and observed increased phosphorylation of ERK on combined stimulation with TGF-β1 and EGF.We also observed persistent phosphorylation of JNK and p38 in the keloid-derived fibroblasts.
Furthermore, we found that treatment with Tranilast can inhibit the phosphorylation of MAPK in the hypertrophic-scar derived fibroblasts.
2. We demonstrated that in contrast to hypertrophic scar-derived and normal skin-derived fibroblasts, keloid-derived fibro-blasts are significantly resistant to both Fas-mediated and staurosporine-induced apoptosis. The caspases-3, -8, and-9 were not activated indicating that the block in the apoptotic pathway in keloid is upstream of the caspases. Addition of transforming growth factor (TGF) -β1 significantly inhibited Fas-mediated apoptosis in hypertrophic scar-derived and normal skin-derived fibroblasts and neutralization of autocrine TGF-β1 with anti-TGF-β1 antibody abrogated the resistance of keloid-derived fibroblasts. This is the first study linking refractory Fas-mediated apoptosis to cellular phenotype in keloids and indicating a pivotal role for the anti-apoptotic effect of TGF-β1 in this resistance. Hence, it becomes important to treat keloids as a separate entity different from hypertrophic scars and enhancement of Fas-sensitivity could be a promising therapeutic target.
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