2011 Fiscal Year Final Research Report
Establishment of new molecular therapy of keloid and elucidation of mechanism of development by inhibition of cAbl tyrosine kinase
| Project/Area Number |
21592297
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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 | Nippon Medical School |
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Principal Investigator |
GHAZIZADEH M. (GHAZIZADEH MOHAMMAD Ghazizadeh) 日本医科大学, 老人病研究所, 准教授 (30190979)
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| Co-Investigator(Kenkyū-buntansha) |
TOSA Mamiko 日本医科大学, 医学部, 助教 (30301568)
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) |
2009 – 2011
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| Keywords | ケロイド / c-Abl / 分子標的治療 |
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| Research Abstract |
We have shown that IL-6 signaling pathway is involved in keloid development. The present study aimed at analysis of the inhibitory effect of small molecule therapeutic agent STI571(imatinib mesylate) and small molecule peptide PD173955 which simultaneously inhibit TGF-β receptor and PDGF receptor and c-Abl tyrosine kinase signaling on keloid. Over-expression of c-Abl, TGF-β receptor, PDGF receptor was found in keloid-derived fiboblasts(KF). Treatment of both normal dermal fibroblasts(NF) and KF cells with STI571 and PD173955 resulted in inhibitory effect on cell growth, migration, ECM-related gene expression, and apoptosis. In addition, inhibition of STI571 and PD173955 abolished the effect on cell growth, collagen synthesis and apoptosis. Implantation of keloid and normal skin tissues into nude mice showed hardening of subcutaneous tissue after 5 weeks which on histological examination revealed accumulation of collagen bundles. Subsequently, we treat these mice with STI571 and PD173955 and evaluate their effects. These results indicate that inhibition of c-Abl tyrosine kinase may prove useful for the development of new molecular therapy of keloid.
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