The role of group IIF-secreted phospholipase A2 in epidermal homeostasis and hyperplasia
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- Kei Yamamoto
- Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan 1
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- Yoshimi Miki
- Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan 1
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- Mariko Sato
- Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan 1
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- Yoshitaka Taketomi
- Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan 1
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- Yasumasa Nishito
- Center for Basic Technology Research, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan 3
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- Choji Taya
- Center for Basic Technology Research, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan 3
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- Kazuaki Muramatsu
- School of Science and Engineering, Tokyo Denki University, Saitama 350-0394, Japan 2
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- Kazutaka Ikeda
- Laboratory for Metabolomics, Institute of Physical and Chemical Research (RIKEN) Center for Integrative Medical Sciences, Kanagawa 230-0045, Japan 4
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- Hiroki Nakanishi
- Research Center for Biosignal, Akita University, Akita 010-8543, Japan 5
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- Ryo Taguchi
- College of Bioscience and Biotechnology, Chubu University, Aichi 487-8501, Japan 6
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- Naotomo Kambe
- Department of Dermatology, Chiba University Graduate School of Medicine, Chiba 260-8677, Japan 7
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- Kenji Kabashima
- Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan 8
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- Gérard Lambeau
- Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275, Centre National de la Recherche Scientifique et Université de Nice-Sophia-Antipolis, 06560 Valbonne, France 9
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- Michael H. Gelb
- Departments of Chemistry and Biochemistry, University of Washington, Seattle, WA 98195 10
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- Makoto Murakami
- Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan 1
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説明
<jats:p>Epidermal lipids are important for skin homeostasis. However, the entire picture of the roles of lipids, particularly nonceramide lipid species, in epidermal biology still remains obscure. Here, we report that PLA2G2F, a functionally orphan-secreted phospholipase A2 expressed in the suprabasal epidermis, regulates skin homeostasis and hyperplasic disorders. Pla2g2f−/− mice had a fragile stratum corneum and were strikingly protected from psoriasis, contact dermatitis, and skin cancer. Conversely, Pla2g2f-overexpressing transgenic mice displayed psoriasis-like epidermal hyperplasia. Primary keratinocytes from Pla2g2f−/− mice showed defective differentiation and activation. PLA2G2F was induced by calcium or IL-22 in keratinocytes and preferentially hydrolyzed ethanolamine plasmalogen-bearing docosahexaenoic acid secreted from keratinocytes to give rise to unique bioactive lipids (i.e., protectin D1 and 9S-hydroxyoctadecadienoic acid) that were distinct from canonical arachidonate metabolites (prostaglandins and leukotrienes). Ethanolamine lysoplasmalogen, a PLA2G2F-derived marker product, rescued defective activation of Pla2g2f−/− keratinocytes both in vitro and in vivo. Our results highlight PLA2G2F as a previously unrecognized regulator of skin pathophysiology and point to this enzyme as a novel drug target for epidermal-hyperplasic diseases.</jats:p>
収録刊行物
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- Journal of Experimental Medicine
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Journal of Experimental Medicine 212 (11), 1901-1919, 2015-10-05
Rockefeller University Press