Extracellular lipid metabolism and skin diseases
| Project/Area Number |
16K18882
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biological pharmacy
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| Research Institution | The University of Tokyo (2017-2018)
Tokyo Metropolitan Institute of Medical Science (2016) |
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Principal Investigator |
Miki Yoshimi 東京大学, 大学院医学系研究科(医学部), 特任研究員 (00632499)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | ホスホリパーゼA2 / 脂質 / 皮膚疾患 / 癌 / 免疫 / 腸内細菌叢 / メタボローム / リポクオリティ / がん / 抗炎症 / 腸管 / 腸内フローラ |
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| Outline of Final Research Achievements |
sPLA2-IID resolves the harmful immune responses by controlling the levels of anti-inflammatory ω3 lipids. However, Pla2g2d-/- mice showed a marked attenuation of skin carcinogenesis. These results underscore a general role of sPLA2-IID as an immunosuppressive sPLA2 that allows the microenvironmental lipid balance toward an anti-inflammatory state, exerting beneficial or detrimental impact depending upon distinct pathophysiological contexts in inflammation and cancer.
While, sPLA2-IIA has been implicated in exacerbation of inflammation by producing lipid mediators and protection against infection by degrading bacterial membranes. We found that sPLA2-IIA deficiency ameliorated skin cancer. Metabolome analyses revealed that sPLA2-IIA affects intestinal microbiota. Thus, our results provide a new aspect of sPLA2-IIA as a regulator of intestinal commensal microbiota, and suggest that perturbation of this process is eventually associated with alterations of host responses in distal organs.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、炎症促進性脂質メディエーター動員酵素としてのPLA2の既成の概念とは異なる脂質代謝酵素の新しい動作原理を提示しており、炎症性疾患の制御および腸内細菌叢の研究領域に新しい概念を導入するものと言える。また、sPLA2-IIAによる腸内細菌とその代謝物の変化を定性的・定量的に捉えたことは、将来的に疾患の発症や予後を予測するための新規診断法の開発や当該代謝物を利用した創薬への応用展開が期待される。近年、ω3脂肪酸や腸内細菌叢の健康への効果が広く認識されつつあり、本研究成果は疾患の制御や予防において身近な概念として普及することが見込まれる。
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Report
(4 results)
Research Products
(36 results)
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[Journal Article] Preventive effect of <i>Dioscorea japonica</i> on squamous cell carcinoma of mouse skin involving down-regulation of prostaglandin E<sub>2</sub> synthetic pathway2018
Author(s)
Tsukayama I, Toda K, Takeda Y, Mega T, Tanaka M, Kawakami Y, Takahashi Y, Kimoto M, Yamamoto K, Miki Y, Murakami M, Suzuki-Yamamoto T.
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Journal Title
Journal of Clinical Biochemistry and Nutrition
Volume: 62
Issue: 2
Pages: 139-147
DOI
NAID
ISSN
0912-0009, 1880-5086
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Lipocalin-type prostaglandin D synthase as a potential biomarker of bovine mastitis2018
Author(s)
Yuki Nagasaki, Erika Kawai, Mitsuki Tanaka, Keisuke Toda, Izumi Tsukayama, Yuki Kawakami, Yoshitaka Takahashi, Masumi Kimoto, Yuka Okazaki, Yoshimi Miki, Kei Yamamoto, Makoto Murakami, Toshiko Suzuki-Yamamoto.
Organizer
59th International Conference on the Bioscience of Lipids
Related Report
Int'l Joint Research
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[Presentation] The two secreted phospholipase A2s PLA2G2F and PLA2G2E play distinct roles in skin homeostasis and diseases.2016
Author(s)
Yamamoto, K., Miki, Y., Sato, H., Taketomi, Y., Lambeau, G., Gelb, M.H., Murakami, M.
Organizer
The 7th International Conference on Phospholipase A2 and Lipid Mediators
Place of Presentation
La Jolla, USA
Year and Date
2016-05-19
Related Report
Int'l Joint Research
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