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)
杉原 平樹 北海道大学, 病院・教授 (20002157)
川嶋 邦裕 北海道大学, 大学院・医学研究科, 助手 (30281801)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥2,400,000 (Direct Cost: ¥2,400,000)
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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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Report
(3 results)
Research Products
(2 results)
