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麝香T对过氧化物酶体增殖物激活受体[PPAR]-α激活、表皮皮肤稳态及真皮透明质酸合成的影响。

The effects of Musk T on peroxisome proliferator-activated receptor [PPAR]-alpha activation, epidermal skin homeostasis and dermal hyaluronic acid synthesis.

作者信息

Kim Seung Hun, Nam Gae Won, Lee Hae Kwang, Moon Seong Joon, Chang Ih Seop

机构信息

Safety and Efficacy Research, Skin Research Institute, Amorepacific Corporation/R&D Center, Yongin, South Korea.

出版信息

Arch Dermatol Res. 2006 Nov;298(6):273-82. doi: 10.1007/s00403-006-0684-y. Epub 2006 Sep 15.

DOI:10.1007/s00403-006-0684-y
PMID:16977445
Abstract

Peroxisome proliferators activated receptors (PPARs) are a family of nuclear hormone receptors that heterodimer with the retinoid X receptor and function as transcriptional regulators of genes. Topically Applied PPAR-alpha agonists possess receptor mediated, pro-differentiating/anti-proliferative effects, lipid metabolism stimulation, and anti-inflammatory activity, which suggest that they could be beneficial for the treatment of a variety of cutaneous diseases. Hyaluronan (HA), a high-molecular-weight linear glycosaminoglycan consisting of alternating D: -glucuronic acid and N-acetyl-D: -glucosamine residues, is one of the major extracellular matrix components in skin. Among the family of HA synthase genes (HAS1, 2, 3) so far identified, one group has demonstrated that the expressions of HAS2 and HAS3 play crucial roles in the regulation of HA synthesis in human skin fibroblasts and keratinocytes, respectively, but the precise regulatory mechanisms are still unknown. We examine Musk T called Ethylene brassylate, Astratone or 1,4-Dioxacycloheptadecane-5,17-dione, which used as just a perfume ingredient, plays a role as PPAR-alpha ligand in vitro and stimulates skin barrier recovery, ceramide synthesis, beta-Glucocerebrosidase, involucrin expression in epidermis in vivo; and examine that Musk T stimulates HAS expression and HA synthesis in human skin fibroblast. Through these experiments, we conclude that Musk T is PPAR-alpha ligand, effects on keratinocyte differentiation, intercellular lipid synthesis in epidermis, HA synthesis stimulation in dermis.

摘要

过氧化物酶体增殖物激活受体(PPARs)是一类核激素受体,与视黄酸X受体形成异二聚体,并作为基因的转录调节因子发挥作用。局部应用的PPAR-α激动剂具有受体介导的促分化/抗增殖作用、脂质代谢刺激作用和抗炎活性,这表明它们可能对多种皮肤病的治疗有益。透明质酸(HA)是一种由交替的D-葡萄糖醛酸和N-乙酰-D-葡萄糖胺残基组成的高分子量线性糖胺聚糖,是皮肤中主要的细胞外基质成分之一。在迄今为止鉴定出的HA合酶基因家族(HAS1、2、3)中,一组研究表明,HAS2和HAS3的表达分别在人皮肤成纤维细胞和角质形成细胞中HA合成的调节中起关键作用,但确切的调节机制仍不清楚。我们研究了麝香T(称为乙酸亚乙酯、Astratone或1,4-二氧杂环十七烷-5,17-二酮),它仅用作香料成分,在体外作为PPAR-α配体发挥作用,并在体内刺激皮肤屏障恢复、神经酰胺合成、β-葡萄糖脑苷脂、表皮中内聚蛋白的表达;并研究了麝香T刺激人皮肤成纤维细胞中HA的表达和HA合成。通过这些实验,我们得出结论,麝香T是PPAR-α配体,对角质形成细胞分化、表皮细胞间脂质合成、真皮中HA合成刺激有影响。

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