REGULATION OF EPIDERMAL LIPID SYNTHESIS

表皮脂质合成的调节

• 批准号: 3159838
• 负责人: KENNETH R FEINGOLD
• 金额: $ 14.28万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-10 至 1995-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3159838
• 关键词: biosynthesis; epithelium; lipogenesis inhibitor; membrane lipids; membrane permeability; skin

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?

描述：（改编自申请人的摘要）尽管脂质