Nicastrin基因突变的反常性痤疮患者皮损Notch-HES信号通路的表达

中华皮肤科杂志 ›› 2016, Vol. 49 ›› Issue (6): 415-419.

Nicastrin基因突变的反常性痤疮患者皮损Notch-HES信号通路的表达

肖学敏¹,李诚让²,何艳艳³,张晓峰⁴,徐浩翔³,王宝玺⁵

1. 福建医科大学附属协和医院
2. 南京中国医学科学院北京协和医学院皮肤病研究所
3. 中国医学科学院皮肤病医院（研究所）
4. 中国医学科学院北京协和医学院皮肤病研究所
5. 中国医学科学院整形外科医院

收稿日期:2015-07-13 修回日期:2015-07-27 发布日期:2016-05-31
通讯作者: 徐浩翔 E-mail:pipi506@stu.xjtu.edu.cn
基金资助:
国家自然科学基金面上项目;国家自然科学基金面上项目;国家自然科学基金面上项目;北京协和医学院协和青年科研基金

Expression of the Notch-HES signaling pathway in lesions of patients with acne inversa harbouring nicastrin gene mutations

Received:2015-07-13 Revised:2015-07-27 Published:2016-05-31
Contact: Hao-Xiang XU E-mail:pipi506@stu.xjtu.edu.cn

摘要/Abstract

摘要：

目的检测nicastrin基因突变的反常性痤疮患者皮损标本中，nicastrin及其下游Notch-HES信号通路蛋白的表达。方法免疫组化法检测nicastrin及 Notch-HES信号通路分子在4例nicastrin基因突变的患者皮损石蜡标本的表达，并用6例正常皮肤组织作对照，同时采用Spearman相关分析，分析nicastrin与Notch-HES信号通路分子表达的相关性。结果 Nicastrin蛋白广泛表达于表皮全层、皮肤附属器,如,毛囊皮脂腺单位、大汗腺及小汗腺。在携带nicastrin基因突变的患者皮损中，表皮及毛囊漏斗部nicastrin表达较正常对照明显减少；同时，Notch-HES信号通路分子表达亦较正常对照明显减少。Nicastrin蛋白与Notch1、Notch3以及HES-1的表达呈明显正相关（r分别为0.831、0.748、0.807，P值分别 < 0.01， < 0.05、 < 0.01），而与Notch2、HES-5的表达之间的相关性，差异无统计学意义（r分别为0.597和0.591，均P > 0.05）。结论 Nicastrin基因突变患者的皮损中nicastrin低表达，且与多种Notch-HES信号通路分子表达呈正相关，提示nicastrin表达减少可能通过影响下游Notch-HES信号通路的表达参与反常性痤疮的发病。

Abstract:

Xiao Xuemin, Li Chengrang, He Yanyan, Zhang Xiaofeng, Xu Haoxiang, Wang Baoxi Department of Dermatology, Union Hospital, Fujian Medical University, Fuzhou 350001, China （Xiao XM）; Department of Dermatology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College; Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing 210042, China （Li CR, He YY, Zhang XF, Xu HX）; Department of Dermatology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100144, China （Wang BX） Corresponding authors: Xu Haoxiang, Email: xbpipi@163.com; Wang Baoxi, Email: wangbx@ncstdlc.org 【Abstract】 Objective To measure s of nicastrin and its downstream Notch-HES signaling pathway-associated proteins in skin lesions of patients with acne inversa harbouring nicastrin gene mutations. Methods An immunohistochemical study was performed to measure the s of nicastrin and Notch-HES signaling pathway-associated proteins in paraffin-embeded skin samples from lesions of 4 patients with acne inversa and confirmed nicastrin mutations and from normal skin of 6 human controls. Spearman correlation analysis was carried out to assess the relationship between the s of nicastrin and Notch-HES signaling pathway-associated proteins. Results In normal control skin samples, nicastrin was widely distributed in the full-thickness epidermis and skin appendages such as pilosebaceous units, apocrine glands and eccrine glands. However, the s of nicastrin and Notch-HES signaling pathway-associated proteins were markedly decreased in the epidermis and hair follicle infundibulum in lesions of patients harbouring nicastrin gene mutations compared with normal control skin. Furthermore, nicastrin was positively correlated with Notch1, Notch3 and HES-1 s （r = 0.831, 0.748 and 0.807, P < 0.01, 0.05 and 0.01 respectively）, but not significantly correlated with Notch2 or HES-5 s （r = 0.597, 0.591 respectively, both P > 0.05）. Conclusion Nicastrin markedly decreases in lesions of patients with acne inversa harbouring nicastrin gene mutations, and is positively correlated with the s of several Notch-HES signaling pathway-associated proteins, suggesting that the decrease in nicastrin may take part in the pathogenesis of acne inversa by influencing the of the downstream Notch-HES signaling pathway.

肖学敏李诚让何艳艳张晓峰徐浩翔王宝玺. Nicastrin基因突变的反常性痤疮患者皮损Notch-HES信号通路的表达[J]. 中华皮肤科杂志, 2016,49(6):415-419. doi:

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