Relationship of epidermal lipogenesis to cutaneous barrier function.
Relationship of epidermal lipogenesis to cutaneous barrier function.
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DOI：
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发表时间：
1987-06
影响因子：
6.5
通讯作者：
G. Grubauer;K. Feingold;P. Elias
中科院分区：
文献类型：
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作者：
G. Grubauer;K. Feingold;P. Elias
虽然哺乳动物角质层中的脂类对皮肤通透性屏障很重要，但调节表皮脂类生物合成的因素却知之甚少。最近的研究表明，皮肤类固醇的合成受皮肤屏障要求的调节，而循环中的类固醇水平并不起作用。皮肤屏障要求是否在总体上调节表皮脂肪生成，以及激活脂质生物合成装置的信号的性质尚不清楚。我们确定了由溶剂(丙酮)、表面活性剂、十二烷基硫酸钠(十二烷基硫酸钠)或必需脂肪酸缺乏症(EFAD)处理引起的皮肤通透性屏障的改变是否引发了对表皮和真皮脂肪生物合成的离散刺激和整体刺激。丙酮处理增加了表皮，但不增加真皮，类固醇和脂肪酸的生物合成在1-4小时大约是对照组的三倍，12小时后恢复正常。十二烷基硫酸钠处理同样刺激了表皮类固醇和脂肪酸的生物合成，但增加没有丙酮处理的动物那么显著。由于塑料闭塞阻止了丙酮处理动物体内预期的从头合成脂肪生物合成的增加，因此水通量可能为从头合成提供了分子信号。最后，与正常人相比，EFAD小鼠还表现出表皮类固醇和脂肪酸生物合成的增加，当通过闭塞使经皮水分丢失正常化时，这种影响也被消除，尽管EFAD正在进行。这些结果表明，皮肤通透性屏障的破坏刺激了限制在表皮的类固醇和脂肪酸生物合成的平行的、全球的促进。由于这种刺激可通过屏障功能的恢复而逆转，因此经皮水梯度可能调节表皮脂肪生成。
Although the lipids of mammalian stratum corneum are known to be important for the cutaneous permeability barrier, the factors that regulate epidermal lipid biosynthesis are poorly understood. Recent studies suggest that cutaneous sterol synthesis is regulated by cutaneous barrier requirements, while the levels of circulating sterols do not play a role. Whether cutaneous barrier requirements regulate epidermal lipogenesis in general and the nature of the signal that activates the lipid biosynthetic apparatus are unknown. We determined whether alterations of the cutaneous permeability barrier, induced by treatment with a solvent (acetone), a surfactant, sodium dodecyl sulfate (SDS), or essential fatty acid deficiency (EFAD), provoked a discrete versus global stimulation of epidermal and dermal lipid biosynthesis. Acetone treatment increased epidermal, but not dermal, sterol and fatty acid biosynthesis approximately threefold over controls at 1-4 hr, which returned to normal after 12 hr. SDS treatment likewise stimulated epidermal sterol and fatty acid biosynthesis, but the increase was less dramatic than in acetone-treated animals. Since plastic occlusion blocked the expected increase in de novo lipid biosynthesis in acetone-treated animals, it is possible that water flux provides the molecular signal for de novo synthesis. Finally, EFAD mice also demonstrated enhanced epidermal sterol and fatty acid biosynthesis in comparison to normals, an effect that also was abolished when transepidermal water loss was normalized by occlusion, despite the presence of ongoing EFAD. These results demonstrate that disruption of the cutaneous permeability barrier stimulates a parallel, global boost in both sterol and fatty acid biosynthesis that is limited to the epidermis. Since such stimulation is reversed by restoration of barrier function, transcutaneous water gradients may regulate epidermal lipogenesis.