REGULATION OF EPIDERMAL LIPID SYNTHESIS

描述：（改编自申请人的摘要）虽然脂质 只占角质层总重量的10%， 在提供皮肤渗透屏障中起关键作用。 研究 已经证明表皮是新生脂质的非常活跃的部位， 合成，这表明屏障功能所需的脂质是 主要来源于表皮脂质合成。 为了支持这一点， 研究人员已经证明，当渗透性屏障被 扰乱存在表皮脂质合成的显著刺激。 最 重要的是，当渗透性屏障的缺陷被修正时， 应用不透水膜，增加表皮 阻止脂质合成。 这表明渗透屏障 需求是调节表皮脂肪生成的关键因素。 此外，这种增加表皮脂质合成的反应， 屏障功能的扰动可能是必不可少的， 角质层脂质和屏障功能恢复正常 局部丙酮处理后。 如果表皮脂质合成 通过人工替换屏障来防止， 丙酮处理后脂质含量和屏障功能均恢复。 这些观察结果使研究人员提出了这样的假设： 皮肤渗透屏障的脂质成分来源于 主要来自局部表皮合成，这种合成受 渗透屏障要求。 在本提案中， 研究人员计划扩展这些观察结果，并回答以下问题 问题：（1）脂质合成在表皮的哪一层 对屏障功能紊乱的反应 (2)是 表皮脂质合成对恢复角质层脂质至关重要 去除角质层后的含量和屏障功能 丙酮处理的脂质？ (3)脂质中哪些特定的酶 生物合成途径被渗透性的干扰所刺激 他们的活动是通过什么机制增加的？ (4)是什么 与屏障破坏相关的调节信号， 表皮脂质合成

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?