{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:38:34Z","timestamp":1792132714253,"version":"4.4.0"},"reference-count":55,"publisher":"Rockefeller University Press","issue":"11","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,10,19]]},"abstract":"<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\u2212\/\u2212 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\u2212\/\u2212 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\u2212\/\u2212 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>","DOI":"10.1084\/jem.20141904","type":"journal-article","created":{"date-parts":[[2015,10,6]],"date-time":"2015-10-06T02:09:26Z","timestamp":1444097366000},"page":"1901-1919","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":100,"title":["The role of group IIF-secreted phospholipase A2 in epidermal homeostasis and hyperplasia"],"prefix":"10.1084","volume":"212","author":[{"given":"Kei","family":"Yamamoto","sequence":"first","affiliation":[{"name":"Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshimi","family":"Miki","sequence":"additional","affiliation":[{"name":"Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Sato","sequence":"additional","affiliation":[{"name":"Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan 1"},{"name":"School of Science and Engineering, Tokyo Denki University, Saitama 350-0394, Japan 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Taketomi","sequence":"additional","affiliation":[{"name":"Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasumasa","family":"Nishito","sequence":"additional","affiliation":[{"name":"Center for Basic Technology Research, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Choji","family":"Taya","sequence":"additional","affiliation":[{"name":"Center for Basic Technology Research, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuaki","family":"Muramatsu","sequence":"additional","affiliation":[{"name":"School of Science and Engineering, Tokyo Denki University, Saitama 350-0394, Japan 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazutaka","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Laboratory for Metabolomics, Institute of Physical and Chemical Research (RIKEN) Center for Integrative Medical Sciences, Kanagawa 230-0045, Japan 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Research Center for Biosignal, Akita University, Akita 010-8543, Japan 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Taguchi","sequence":"additional","affiliation":[{"name":"College of Bioscience and Biotechnology, Chubu University, Aichi 487-8501, Japan 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naotomo","family":"Kambe","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Chiba University Graduate School of Medicine, Chiba 260-8677, Japan 7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Kabashima","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan 8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9rard","family":"Lambeau","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie Mol\u00e9culaire et Cellulaire, UMR7275, Centre National de la Recherche Scientifique et Universit\u00e9 de Nice-Sophia-Antipolis, 06560 Valbonne, France 9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Gelb","sequence":"additional","affiliation":[{"name":"Departments of Chemistry and Biochemistry, University of Washington, Seattle, WA 98195 10"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Murakami","sequence":"additional","affiliation":[{"name":"Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan 1"},{"name":"CREST, Japan Agency for Medical Research and Development (AMED) and Japan Science and Technology Agency (JST), Tokyo 100-0004, Japan 11"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2015,10,5]]},"reference":[{"key":"2023072602382732700_bib1","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1161\/ATVBAHA.112.300309","article-title":"Group X secreted phospholipase A2 limits the development of atherosclerosis in LDL receptor-null mice","volume":"33","author":"Ait-Oufella","year":"2013","journal-title":"Arterioscler. 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