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Nicotinic acetylcholine receptor stimulation impairs epidermal permeability barrier function and recovery and modulates cornified envelope proteins.

机译:烟碱乙酰胆碱受体刺激损害表皮渗透性屏障功能和恢复并调节颅骨包膜蛋白。

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To characterize how nicotinic acetylcholine receptors (nAChRs) influence epidermal barrier function and recovery following prolonged stress or direct nAChR activation or antagonism.Mice were subjected to psychological stress or treated topically with nAChR agonist or antagonist for 3 days. We assessed barrier permeability and recovery by measuring transepidermal water loss (TEWL) before and after barrier disruption. In parallel, we analyzed the production and localization of several epidermal cornified envelope proteins in mouse skin and in human EpiDerm? organotypic constructs stimulated with a nAChR agonist (nicotine) and/or a nAChR selective antagonist (α-bungarotoxin).We determined that psychological stress in mice impairs barrier permeability function and recovery, an effect that is reversed by application of the α7 selective nAChR antagonist, α-bungarotoxin (Bung). In the absence of stress, both topical nicotine or Bung treatment alone impaired barrier permeability. We further observed that stress, topical nicotine, or topical Bung treatment in mice influenced the abundance and/or localization of filaggrin, loricrin, and involucrin. Similar alterations in these three major cornified envelope proteins were observed in human EpiDerm? cultures.Perceived psychological stress and nicotine usage can both initiate or exacerbate several dermatoses by altering the cutaneous permeability barrier. Modulation of nAChRs by topical agonists or antagonists may be used to improve epidermal barrier function in skin diseases associated with defects in epidermal barrier permeability.
机译:表征烟碱乙酰胆碱受体(NACHRS)如何影响表皮屏障函数和恢复在长期应激或直接的NACHR活化或拮抗剂之后进行心理压力或用NACHR激动剂或拮抗剂局部处理3天。我们通过在屏障中断之前和之后测量Transepidermal水分损失(TEWL)评估阻挡渗透性和恢复。并行地,我们分析了几种表皮角膜囊蛋白在小鼠皮肤和人体表皮中的产生和定位?用NACHR激动剂(尼古丁)和/或NACHR选择性拮抗剂(α-BUNGAROTOXIN)刺激的有机型构建体。我们确定小鼠的心理应激损害屏障渗透功能和恢复,通过应用α7选择性NACHR拮抗剂逆转的效果,α-bungarotoxin(bung)。在没有压力的情况下,局部尼古丁或肿胀处理单独受损屏障渗透性。我们进一步观察到,小鼠中的应力,局部尼古丁或局部肿瘤治疗影响了Fil​​aggrin,鲁兰林素和甘草的丰富和/或定位。在人体表皮中观察到这三个主要的颅骨状包膜蛋白的类似改变?培养物。通过改变皮肤渗透性屏障,人们可以发起或加剧几种皮肤的心理压力和尼古丁使用。通过局部激动剂或拮抗剂的调制可用于改善与表皮阻隔渗透性缺陷相关的皮肤病中的表皮阻挡功能。

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