REGULATION OF EPIDERMAL LIPID SYNTHESIS

描述：(改编自申请人的摘要)尽管血脂 仅占其角质层总重量的10% 在提供皮肤渗透性屏障方面的关键作用。研究 已经证明了表皮是新生脂质的一个非常活跃的部位 合成，表明屏障功能所需的脂类是 主要来源于表皮脂肪的合成。为了支持这一点， 研究人员已经证明，当渗透屏障是 受扰时有明显的刺激表皮脂合成。多数 重要的是，当渗透性屏障的缺陷通过 应用防水防渗膜，增加了表皮 阻止了脂肪的合成。这表明渗透性屏障 需求是调节表皮脂肪生成的关键因素。 此外，这种表皮脂肪合成的增加是对 屏障功能的紊乱可能是恢复功能所必需的 角质层脂质与屏障功能的恢复 在局部丙酮治疗后。如果表皮脂肪合成是 通过人工替换屏障来防止，无论是角质层 丙酮治疗后，脂质含量和屏障功能均未恢复。 这些观察结果使研究人员得出了这样的假设： 皮肤通透性屏障的脂质成分是由 主要来自局部表皮的合成，这种合成是由 渗透性屏障要求。在本提案中， 研究人员计划扩大这些观察，并回答以下问题 问题：(1)表皮的哪一层是脂类合成 应激对屏障功能的干扰？(2)是 表皮脂肪合成在角质层脂肪修复中的作用 角质层去除后的内容物和屏障功能 丙酮处理的脂类？(3)脂类中的哪些特定酶 生物合成途径受到通透性干扰的刺激 他们的活动是通过什么机制增加的？(4)什么是 与屏障破坏相关的调节信号刺激 表皮脂肪合成？

DESCRIPTION: (Adapted from the applicant's abstract) Although lipids account for only 10 percent of the total stratum corneum weight they play a critical role in providing for the cutaneous permeability barrier. Studies have demonstrated that the epidermis is a very active site of de novo lipid synthesis, suggesting that the lipids necessary for barrier function are derived primarily from epidermal lipid synthesis. In support of this the investigators have demonstrated that when the permeability barrier is disturbed there is a marked stimulation of epidermal lipid synthesis. Most importantly, when the defect in permeability barrier is corrected by the application of a water-impermeable membrane, the increase in epidermal lipid synthesis is prevented. This suggests that permeability barrier requirements is a crucial factor that regulates epidermal lipogenesis. Moreover, this increase in epidermal lipid synthesis in response to pertubations in barrier function may be essential in the restoration of stratum corneum lipids and the return of barrier function to normal following topical acetone treatment. If epidermal lipid synthesis is prevented by artifically replacing the barrier, neither stratum corneum lipid content nor barrier function recovers following acetone treatment. These observations have led the investigators to the hypothesis that the lipid components of the cutaneous permeability barrier are derived primarily from local epidermal synthesis and this synthesis is regulated by permeability barrier requirements. In the present proposal the investigators plan to extend these observations and answer the following questions: (1) In which layer of the epidermis is lipid synthesis stimulated in response to disturbances in barrier function? (2) Is epidermal lipid synthesis crucial in restoring stratum corneum lipid content and barrier function following the removal of stratum corneum lipids by acetone treatment? (3) Which specific enzymes in the lipid biosynthetic pathways are stimulated by disturbances in the permeability barrier and by what mechanisms are their activities increased? (4) What is the regulatory signal associated with barrier disruption that stimulates epidermal lipid synthesis?