Laboratory of Microenvironmental and Metabolic Health Science, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan; AMED-CREST, Japan Agency for Medical Research and Development, 1-7-1 Otemachi, Chiyoda-ku, Tokyo 100-0004, Japan.
Laboratory of Microenvironmental and Metabolic Health Science, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Jun;1864(6):803-818. doi: 10.1016/j.bbalip.2018.08.014. Epub 2018 Aug 31.
Among the 11 members of the secreted phospholipase A (sPLA) family, group IID, IIE, IIF and III sPLAs (sPLA-IID, -IIE, -IIF and -III, respectively) are "new" isoforms in the history of sPLA research. Relative to the better characterized sPLAs (sPLA-IB, -IIA, -V and -X), the enzymatic properties, distributions, and functions of these "new" sPLAs have remained obscure until recently. Our current studies using knockout and transgenic mice for a nearly full set of sPLAs, in combination with comprehensive lipidomics, have revealed unique and distinct roles of these "new" sPLAs in specific biological events. Thus, sPLA-IID is involved in immune suppression, sPLA-IIE in metabolic regulation and hair follicle homeostasis, sPLA-IIF in epidermal hyperplasia, and sPLA-III in male reproduction, anaphylaxis, colonic diseases, and possibly atherosclerosis. In this article, we overview current understanding of the properties and functions of these sPLAs and their underlying lipid pathways in vivo.
在分泌型磷脂酶 A（sPLA）家族的 11 个成员中，I 组、IID、IIE、IIF 和 III 型 sPLA（分别为 sPLA-IID、-IIE、-IIF 和 -III）是 sPLA 研究历史上的“新”同工酶。相对于表征较好的 sPLA（sPLA-IB、-IIA、-V 和 -X），这些“新”sPLA 的酶学特性、分布和功能直到最近才变得清晰。我们目前使用几乎全套 sPLA 的基因敲除和转基因小鼠进行的研究，结合全面的脂质组学分析，揭示了这些“新”sPLA 在特定生物学事件中的独特和不同的作用。因此，sPLA-IID 参与免疫抑制，sPLA-IIE 参与代谢调节和毛囊稳态，sPLA-IIF 参与表皮增生，sPLA-III 参与雄性生殖、过敏反应、结肠疾病，可能还参与动脉粥样硬化。在本文中，我们概述了目前对这些 sPLA 的特性和功能及其体内脂质途径的理解。
