Genetics of Development and Disease Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Biol Chem. 2013 Jun 21;288(25):18381-91. doi: 10.1074/jbc.M113.478420. Epub 2013 May 1.
Sphingosine 1-phosphate (S1P) is a bioactive lipid whose levels are tightly regulated by its synthesis and degradation. Intracellularly, S1P is dephosphorylated by the actions of two S1P-specific phosphatases, sphingosine-1-phosphate phosphatases 1 and 2. To identify the physiological functions of S1P phosphatase 1, we have studied mice with its gene, Sgpp1, deleted. Sgpp1(-/-) mice appeared normal at birth, but during the 1st week of life they exhibited stunted growth and suffered desquamation, with most dying before weaning. Both Sgpp1(-/-) pups and surviving adults exhibited multiple epidermal abnormalities. Interestingly, the epidermal permeability barrier developed normally during embryogenesis in Sgpp1(-/-) mice. Keratinocytes isolated from the skin of Sgpp1(-/-) pups had increased intracellular S1P levels and displayed a gene expression profile that indicated overexpression of genes associated with keratinocyte differentiation. The results reveal S1P metabolism as a regulator of keratinocyte differentiation and epidermal homeostasis.
鞘氨醇 1-磷酸（S1P）是一种生物活性脂质，其水平受到其合成和降解的严格调节。在细胞内，S1P 通过两种 S1P 特异性磷酸酶，即鞘氨醇-1-磷酸磷酸酶 1 和 2 的作用被去磷酸化。为了确定 S1P 磷酸酶 1 的生理功能，我们研究了其基因 Sgpp1 缺失的小鼠。Sgpp1(-/-) 小鼠在出生时看起来正常，但在生命的第一周，它们表现出生长迟缓并出现脱皮，大多数在断奶前死亡。Sgpp1(-/-) 幼鼠和存活的成年小鼠都表现出多种表皮异常。有趣的是，Sgpp1(-/-) 小鼠的表皮渗透性屏障在胚胎发育过程中正常发育。从 Sgpp1(-/-) 幼鼠皮肤中分离出的角质形成细胞细胞内 S1P 水平升高，并表现出基因表达谱，表明与角质形成细胞分化相关的基因表达过度。结果表明 S1P 代谢是角质形成细胞分化和表皮动态平衡的调节剂。
