Development of fibrosis suppression therapies targeting enzyme-activating molecules for lysyl oxidase
| Project/Area Number |
18H02960
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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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| Review Section |
Basic Section 56070:Plastic and reconstructive surgery-related
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| Research Institution | Kyoto University |
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Principal Investigator |
Noda Kazuo 京都大学, 医学研究科, 客員研究員 (50633161)
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| Co-Investigator(Kenkyū-buntansha) |
中邨 智之 関西医科大学, 医学部, 教授 (20362527)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2021: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
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| Keywords | Fibulin-4 / コラーゲンクロスリンク / 繊維化 / 真皮組織 / 創傷治癒 / 線維化 |
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| Outline of Final Research Achievements |
Adult mice with reduced expression of Fibulin-4 in the dermis were generated. The back skin of these mice was harvested for phenotypic analysis of the dermis. The back skin of mice with reduced dermal Fibulin-4 expression showed a tendency towards defective formation of elastic and collagen fibres and reduced dermal thickness compared to normal mouse back skin.
Although we were able to show that reduced Fibulin-4 expression results in the hypoplasia of collagen fibres during normal dermal development, further studies are needed to determine whether the suppression of Fibulin-4 expression during wound healing suppresses fibrosis.
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| Academic Significance and Societal Importance of the Research Achievements |
異常なコラーゲン線維形成の原因の一つと考えられる線維化を抑制するために、コラーゲン架橋酵素LOXの酵素活性を制御するための治療標的分子として、Fibulin-4が候補となりうる可能性を示唆する結果が得られた。
LOXの酵素活性化を阻害する分子として、古くからβアミノプロピオニトリル(BAPN)が知られてが、BAPNには神経毒性などの副作用があるため臨床使用することは難しい。そこで、LOXの酵素活性化に必須の分子Fibulin-4を標的としてLOXの機能を阻害することができれば、線維化治療の標的分子になりうる。繊維化病変に対する治療薬は少ないので、治療薬ができればその社会的意義は大きいと思われる。
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Report
(5 results)
Research Products
(7 results)
