Sakai Shota, Makino Asami, Nishi Akihito, Ichikawa Takeshi, Yamashita Tadashi, Taniguchi Makoto, Tokudome Yoshihiro, Hirabayashi Yoshio, Akiyama Masashi, Crumrine Debra, Uchida Yoshikazu, Elias Peter M, Tsuchida Tetsuya, Hamanaka Sumiko
Laboratory of Biomembrane and Biofunctional Chemistry, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan.
Department of Biochemistry & Cell Biology, National Institute of Infectious Diseases, Tokyo, Japan.
Skin Pharmacol Physiol. 2021;34(5):246-252. doi: 10.1159/000515608. Epub 2021 Apr 29.
Sphingomyelin (SM) is a constituent of cellular membranes, while ceramides (Cer) produced from SM on plasma membranes serve as a lipid mediator that regulates cell proliferation, differentiation and apoptosis. In the skin, SM also is a precursor of Cer, an important constituent of epidermal permeability barrier. We investigated the role of epidermal SM synthase (SMS)2, an isoform of SMS, which modulates SM and Cer levels on plasma membranes. Although SMS2-knockout (SMS2-KO) mice were not neonatal lethal, an ichthyotic phenotype with epidermal hyperplasia and hyperkeratosis was evident at birth, which persisted until 2 weeks of age. These mice showed abnormal lamellar body morphology and secretion, and abnormal extracellular lamellar membranes in the stratum corneum (SC). These abnormalities were no longer evident by 4 weeks of age in SMS2-KO mice. Our study suggests that: 1) exposure to a dry terrestrial environment initiates compensatory responses, thereby normalizing epidermal ichthyotic abnormalities; and 2) that a non-lethal gene abnormality can cause an ichthyotic skin phenotype.
鞘磷脂（SM）是细胞膜的组成成分，而质膜上由SM产生的神经酰胺（Cer）作为一种脂质介质，可调节细胞增殖、分化和凋亡。在皮肤中，SM也是Cer的前体，Cer是表皮渗透屏障的重要组成成分。我们研究了表皮鞘磷脂合酶（SMS）2的作用，SMS2是SMS的一种同工型，可调节质膜上的SM和Cer水平。虽然SMS2基因敲除（SMS2-KO）小鼠并非出生即致死，但出生时即出现明显的鱼鳞病表型，伴有表皮增生和角化过度，这种表型一直持续到2周龄。这些小鼠表现出板层小体形态和分泌异常，以及角质层（SC）细胞外板层膜异常。在SMS2-KO小鼠4周龄时，这些异常不再明显。我们的研究表明：1）暴露于干燥的陆地环境会引发代偿反应，从而使表皮鱼鳞病异常恢复正常；2）非致死性基因异常可导致鱼鳞病皮肤表型。
