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
(71 results)
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[Journal Article] Group X Secreted Phospholipase A2 Releases ω3 Polyunsaturated Fatty Acids, Suppresses Colitis, and Promotes Sperm Fertility.2016
Author(s)
Murase R, Sato H, Yamamoto K, Ushida A, Nishito Y, Ikeda K, Kobayashi T, Yamamoto T, Taketomi Y, Murakami M.
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Journal Title
J Biol Chem.
Volume: 291
Issue: 13
Pages: 6895-6911
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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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., Nakanishi, H., Taguchi, R., Kambe, N., Kabashima, K., Lambeau, G., Gelb, M.H., and Murakami, M
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Journal Title
J. Exp. Med.
Volume: 212
Issue: 11
Pages: 1901-1919
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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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 PLA2G32015
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
Issue: 12
Pages: 2321-2332
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Calpastatin counteracts pathological angiogenesis by inhibiting suppressor of cytokine signaling 3 degradation in vascular endothelial cells.2015
Author(s)
Miyazaki, T., Taketomi, Y., Saito, Y., Hosono, T., Lei, X.F., Kim-Kaneyama, J.R., Arata, S., Takahashi, H., Murakami, M., and Miyazaki, A.
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Journal Title
Circ. Res.
Volume: 116
Issue: 7
Pages: 1170-1181
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] ERK1/2 antagonize AMPK-dependent regulation of FcεRI-mediated mast cell activation and anaphylaxis.2014
Author(s)
Hwang, S.K., Lu, Y., Li, X., Kim, Y.D., Cho, Y.S., Jahng, Y., Son, J.K., Lee, Y.J., Kang, W., Taketomi, Y., Murakami, M., Moon, T.C., and Chang, H.W.
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Journal Title
J. Allergy Clin. Immunol.
Volume: 134
Issue: 3
Pages: 714-721
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The adipocyte-inducible secreted phospholipases PLA2G5 and PLA2G2E play distinct roles in obesity.2014
Author(s)
Sato H, Taketomi Y, Ushida A, Isogai Y, Kojima T, Hirabayashi T, Miki Y, Yamamoto K, Nishito Y, Kobayashi T, Ikeda K, Taguchi R, Hara S, Ida S, Miyamoto Y, Watanabe M, Baba H, Miyata K, Oike Y, Gelb MH, Murakami M.
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Journal Title
Cell Metab.
Volume: 20
Issue: 1
Pages: 119-132
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Prostaglandin E2-EP3 signaling induces inflammatory swelling by mast cell activation.2014
Author(s)
Morimoto, K., Shirata, N., Taketomi, Y., Tsuchiya, S., Segi-Nishida, E., Inazumi, T., Kabashima, K., Tanaka, S., Murakami, M., Narumiya, S., and Sugimoto, Y.
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Journal Title
J. Immunol.
Volume: 192
Issue: 3
Pages: 1130-1137
DOI
Related Report
Peer Reviewed
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[Journal Article] Lymphoid tissue phospholipase A2 group IID resolves contact hypersensitivity by driving antiinflammatory lipid mediators.2013
Author(s)
Miki Y, Yamamoto K, Taketomi Y, Sato H, Shimo K, Kobayashi T, Ishikawa Y, Ishii T, Nakanishi H, Ikeda K, Taguchi R, Kabashima K, Arita M, Arai H, Lambeau G, Bollinger JM, Hara S, Gelb MH, Murakami M.
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Journal Title
J Exp Med.
Volume: 210
Issue: 6
Pages: 1217-1234
DOI
Related Report
Peer Reviewed
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[Journal Article] AMP-activated protein kinase negatively regulates FcεRI-mediated mast cell signaling and anaphylaxis in mice.2013
Author(s)
Hwang SL, Li X, Lu Y, Jin Y, Jeong YT, Kim YD, Lee IK, Taketomi Y, Sato H, Cho YS, Murakami M, Chang HW.
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Journal Title
J Allergy Clin Immunol.
Volume: 132
Issue: 3
Pages: 729-736
DOI
Related Report
Peer Reviewed
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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
Related Report
Int'l Joint Research
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