Elucidation of Wnt5a signal transduction mechanism(s) in keloid and application of molecular targeted therapy
| Project/Area Number |
24592722
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Plastic surgery
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| Research Institution | Nippon Medical School |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
TOSA Mamiko 日本医科大学, 医学部, 助教 (30301568)
清水 一 日本医科大学, 付置研究所, その他 (60398873)
村上 正洋 日本医科大学, 医学部, 准教授 (00239500)
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| Co-Investigator(Renkei-kenkyūsha) |
SHIMIZU Hajime 日本医科大学, 老人病研究所, マネージメントサポートスタッフ (60398873)
MURAKAMI Masahiro 日本医科大学, 医学部, 准教授 (00239500)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | Keloid pathogenesis / Wnt5a / beta-catenin / EMT / Wnt signal-related genes / 分子標的治療 / keloid / Wnt signaling / β-catenin / keloid pathogenesis / wound healing / frizzeld4 / ROR2 / frizzled4 |
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| Outline of Final Research Achievements |
We studied the expression and function of Wnt5a considering frizzled4 receptor, ROR2, Wnt signal downstream targets (GSK3-beta and beta-catenin) as well as epithelial-mesenchymal transition (EMT) markers and 84 Wnt signal-related genes in primary fibroblast cultures and tissue samples from keloid (KF) and normal dermis (NF)using molecular biology, immunohistochemical and RT2 Profiler PCR Array methods. A high expression of Wnt5a and beta-catenin was found in KF compared to NF. Treatment of NF and KF with recombinant Wnt5a peptide resulted in an increase in total beta-catenin and phosphorylated beta-catenin at Ser33/37/Thr41 but no significant change in phosphorylated beta-catenin at Ser45/Thr41 positions. Several Wnt signal-related genes were also upregulated. In addition, evidence for EMT in keloid was observed. These findings highlight a potential role for a Wnt/beta-catenin pathway triggered by Wnt5a in keloid pathogenisis and development of molecular targeted therapy for keloid.
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Report
(4 results)
Research Products
(9 results)
