2005 Fiscal Year Final Research Report Summary
Novel gene therapy of keloid by using siRNA
| Project/Area Number |
16591791
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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 |
Plastic surgery
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
SASAKI Satoru Hokkaido Univ., Grad.School of Medicine, Lecturer, 大学院・医学研究科, 講師 (40301907)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Yuhei Hokkaido Univ., Grad.School of Medicine, Prof., 大学院・医学研究科, 教授 (70271674)
OYAMA Akihiko Hokkaido Univ., Hokkaido University Hospital, Inst., 助手 (70374486)
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| Project Period (FY) |
2004 – 2005
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| Keywords | keloid / siRNA / TGF-β1 / MIF / gene therapy / PGE_2 / cAMP |
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| Research Abstract |
We hypothesized that gene therapy by using small interfering RNA (siRNA) would be valid on keloid. Firstly, we tried to knockdown TGF- 1 mRNA by transduction of siRNA. As a result, TGF- 1 production was down-regulated. We found that collgen production and cell growth in keloid-derived fibroblasts (KF) down-regulated by decreased TGF- 1 production. Therefore we believe that gene therapy by using siRNA may be useful for the treatment of keloid.
In this study, We investigated the metabolism of arachidonic acid in normal skin-derived fibroblasts (NF) as well as in keloid-derived fibroblasts (KF) in response to macrophage migration inhibitory factor (MIF), a pluripotent cytokine. We found that MIF enhanced cyclooxygenase-2 (COX-2) activity in NF more than in KF. Consistent with this finding, prostaglandin E_2 (PGE_2), an antifibrogenic molecule, was more significantly increased in NF than in KF by MIF treatment. As regarding E prostanoid receptor 2 (EP2), the level of expression was significantly lower in KF than in NF. On the other hand, Forskolin, a direct activator of adenylcyclase, decreased collagen synthesis in both NF and KF, which indicates that cAMP plays an important role in regulating collagen synthesis. Since PGE_2 induces cAMP production, it is conceivable that increased collagen synthesis in KF might be due to decreased PGE_2 and cAMP production. These findings may aid in the development of a therapeutic strategy for the regulation of collagen synthesis in keloid fibroblasts.
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