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淀粉样前体蛋白的过表达促进脂溢性角化病的发生,并与皮肤老化有关。

Overexpression of Amyloid Precursor Protein Promotes the Onset of Seborrhoeic Keratosis and is Related to Skin Ageing.

机构信息

Department of Dermatology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550001, P.R, China.

出版信息

Acta Derm Venereol. 2018 Jun 8;98(6):594-600. doi: 10.2340/00015555-2911.

Abstract

Seborrhoeic keratosis (SK) is an age-related skin disease. Amyloid precursor protein (APP) plays an important role in the pathogenesis of age-related Alzheimer's disease. The aim of this study was to elucidate the expression characteristics of APP in SK tissues (n = 50), and explore whether the production of APP is related to the onset of SK and skin ageing, including ultraviolet (UV)-induced ageing, as observed in normal skin (n = 79). The results of immunohistochemistry, Western blotting and quantitative real-time PCR showed that APP and its downstream products (i.e. amyloid-β42) were more highly expressed in SK than in paired adjacent normal skin tissues. In contrast, the expression of its key secretase (i.e. β-secretase1) was generally low. Furthermore, APP expression was higher in UV-exposed than non-exposed skin sites, and expression in the older age group (61-85 years) was greater than that in the younger age group (41-60 years) in SK tissues (p<0.05). APP expression correlated positively with age in epidermis (p<0.05), but not in dermis. These findings suggest that overexpression of APP may promote the onset of SK and is a marker of skin ageing and UV damage. Further research will elucidate whether therapeutic mitigation of increased levels of APP in the skin might delay the onset of SK and skin ageing.

摘要

脂溢性角化病(SK)是一种与年龄相关的皮肤疾病。淀粉样前体蛋白(APP)在与年龄相关的阿尔茨海默病的发病机制中起着重要作用。本研究旨在阐明 APP 在 SK 组织(n=50)中的表达特征,并探讨 APP 的产生是否与 SK 和皮肤衰老有关,包括在正常皮肤(n=79)中观察到的紫外线(UV)诱导的衰老。免疫组织化学、Western blot 和定量实时 PCR 的结果表明,APP 及其下游产物(即淀粉样蛋白-β42)在 SK 中的表达高于配对的相邻正常皮肤组织。相比之下,其关键蛋白酶(即β-分泌酶 1)的表达通常较低。此外,APP 在暴露于 UV 的皮肤部位的表达高于非暴露部位,在 SK 组织中,年龄较大组(61-85 岁)的表达高于年龄较小组(41-60 岁)(p<0.05)。APP 表达与表皮的年龄呈正相关(p<0.05),但与真皮无关。这些发现表明,APP 的过度表达可能促进 SK 的发生,是皮肤衰老和 UV 损伤的标志物。进一步的研究将阐明在皮肤中减少 APP 水平的治疗是否可能延迟 SK 和皮肤衰老的发生。

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