Extracellular lipid metabolism and skin diseases

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K18882
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: The University of Tokyo (2017-2018); Tokyo Metropolitan Institute of Medical Science (2016)
• 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)
• Project Period (FY): 2016-04-01 – 2019-03-31
• 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

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.

Free Research Field

脂質生化学

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。