New insights into the roles of secreted phospholipase A2 in allergy, atherosclerosis, and cancer
Project/Area Number |
25460087
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Biological pharmacy
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Research Institution | Tokyo Metropolitan Institute of Medical Science |
Principal Investigator |
TAKETOMI Yoshitaka 公益財団法人東京都医学総合研究所, 生体分子研究分野, 主席研究員 (40365804)
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Research Collaborator |
MURAKAMI Makoto
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | 脂質代謝 / アレルギー / 動脈硬化 / 大腸癌 / ホスホリパーゼA2 / 脂質メディエーター / 癌 / リン脂質 / 分泌性ホスホリパーゼA2 / マスト細胞成熟 / リゾホスファチジン酸 / アナフィラキシー / 好塩基球 / IgE依存性慢性アレルギー性炎症 / LDL変性 |
Outline of Final Research Achievements |
Phosholipas A2 (PLA2) is a group of enzyme that hydrolyze the phospholipids to yield fatty acids and lysophospholipids. Here we have found that the paracrine PGD2 circuit driven by PLA2G3, a secreted PLA2 isoform, is a previously unrecognized lipid-orchestrated pathway linked to allergy and uncovers a missing microenvironmental cue underlying the proper maturation of mast cells. In addition to that, we identified the LPA-LPA1 axis as another lipid-orchestrated pathway toward mast cell maturation. Besides the regulation of mast cell and allergy, accumulating evidence suggests that PLA2G3 generally acts as a paracrine coordinator of various pathophysiological events as metabolic disorders and inflammatory bowl diseases. Our results highlight that PLA2G3 is bona fide pro-atherogenic sPLA2 that facilitates atherosclerosis through modifying LDL and promotes colitis and colon cancer by mobilizing lysophospholipids, providing a rationale for PLA2G3 to be a novel drug target of these diseases.
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Report
(4 results)
Research Products
(72 results)
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[Journal Article] The role of group IIF secreted phospholipase A2 in epidermal homeostasis and hyperplasia.2015
Author(s)
Yamamoto K, Miki Y, Sato M, Taketomi Y, Nishito Y, Taya C, Muramatsu K, Ikeda K, Taguchi R, Kambe N, Kabashima K, Lambeau G, Gelb MH, Murakami M.
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Journal Title
J Exp Med
Volume: 212
Pages: 1901-1919
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Phospholipase A2 group III and group X have opposing associations with prognosis in colorectal cancer.2015
Author(s)
Kazama S, Kitayama J, Hiyoshi M, Taketomi Y, Murakami M, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Kawai K, Hata K, Yamaguchi H, Nozawa H, Ishihara S, Sunami E, Watanabe T.
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Journal Title
Anticancer Res
Volume: 35
Pages: 2983-2990
Related Report
Peer Reviewed
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[Journal Article] Primary cilium suppression by SREBP1c involves distortion of vesicular trafficking by PLA2G3.2015
Author(s)
Gijs HL, Willemarck N, Vanderhoydonc F, Khan NA, Dehairs J, Derua R, Waelkens E, Taketomi Y, Murakami M, Agostinis P, Annaert W, Swinnen JV.
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Journal Title
Mol Biol Cell
Volume: 26
Pages: 2321-2332
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Presentation] 脂質メディエーターと免疫調節.2016
Author(s)
武富芳隆, 村上誠.
Organizer
日本薬学会第136年会
Place of Presentation
パシフィコ横浜(神奈川県横浜市)
Year and Date
2016-03-26 – 2016-03-29
Related Report
Invited
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[Presentation] Skin abnormalities in group III sPLA2-deficient mice.2015
Author(s)
Taketomi Y, Endo Y, Yamamoto K, Kobayashi T, Murakami M.
Organizer
Bioactive Lipids in Cancer, Inflammation, and Related Diseases (14th International Conference)
Place of Presentation
SOFITEL CHAIN BRIDGE HOTEL (Budapest, Hungary)
Year and Date
2015-07-12 – 2015-07-15
Related Report
Int'l Joint Research
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