Functions of peroxisome proliferator-activated receptors (PPAR) in skin homeostasis
Functions of peroxisome proliferator-activated receptors (PPAR) in skin homeostasis
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DOI：
10.1007/s11745-004-1335-y
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发表时间：
2004-11-01
期刊：
影响因子：
1.9
通讯作者：
Wahli, W
中科院分区：
文献类型：
--
作者：
Di-Poï, N;Michalik, L;Wahli, W
过氧化物酶体增殖物激活受体（peroxisome proliferator-activated receptor，PPAR）是一种配体激活的转录因子，属于核激素受体家族。在脊椎动物中发现了具有不同组织分布和细胞功能的三种同种型（PPARalpha、PPARbeta或delta和PPARgamma）。所有三种PPAR同种型在啮齿动物和人类皮肤中表达。由于它们在其他细胞类型中的脂质代谢中的已知功能，最初研究它们在皮肤中建立渗透性屏障中的可能功能。在体外研究中使用特定的过氧化物酶体增殖体激活物受体激动剂和在小鼠体内基因破坏的方法确实表明了一个重要的贡献，PPARalpha的表皮屏障的形成和皮脂腺细胞分化。PPARgamma同种型在刺激皮脂细胞发育和脂肪生成中起作用，但似乎不有助于表皮组织分化。第三种同种型PPARbeta调节皮脂腺细胞分化的晚期阶段，并且是在啮齿动物和人类中刺激这些细胞中脂质产生的最有效同种型。此外，在正常和炎症条件下，PPAR β活化在角膜细胞中具有促分化作用。最后，初步的研究还指出，在毛囊生长和黑素细胞分化的潜在作用的过氧化物酶体增殖物激活物受体。通过其对皮肤中细胞增殖和分化的不同生物学效应，PPAR激动剂或拮抗剂可为治疗以炎症、细胞过度增殖和异常分化为特征的各种皮肤病症提供有趣的机会。
The peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors that belong to the nuclear hormone receptor family. Three isotypes (PPARalpha, PPARbeta or delta, and PPARgamma) with distinct tissue distributions and cellular functions have been found in vertebrates. All three PPAR isotypes are expressed in rodent and human skin. They were initially investigated for a possible function in the establishment of the permeability barrier in skin because of their known function in lipid metabolism in other cell types. In vitro studies using specific PPAR agonists and in vivo gene disruption approaches in mice indeed suggest an important contribution of PPARalpha in the formation of the epidermal barrier and in sebocyte differentiation. The PPARgamma isotype plays a role in stimulating sebocyte development and lipogenesis, but does not appear to contribute to epidermal tissue differentiation. The third isotype, PPARbeta, regulates the late stages of sebaceous cell differentiation, and is the most effective isotype in stimulating lipid production in these cells, both in rodents and in humans. in addition, PPARbeta activation has pro-differentiating effects in kera-tinocytes under normal and inflammatory conditions. Finally, preliminary studies also point to a potential role of PPAR in hair follicle growth and in melanocyte differentiation. By their diverse biological effects on cell proliferation and differentiation in the skin, PPAR agonists or antagonists may offer interesting oppotunities for the treatment of various skin disorders characterized by inflammation, cell hyperproliferation, and aberrant differentiation.