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

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

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Notchl、Notch3以及HES一1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一5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。

Objective To measure expressions 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 immunohistoehemieal study was performed to measure the expressions of nicastrin and Notch-liES signaling pathwayassociated 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 expressions 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 expressions 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 expression was positively correlated with Notchl, Notch3 and HES-1 expressions （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 expressions （r = 0.597, 0.591 respectively, both P 〉 0.05）. Conclusion Nicastrin expression markedly decreases in lesions of patients with acne inversa harbouring nicastrin gene mutations, and is positively correlated with the expressions of several Notch-liES signaling pathway-associated proteins, suggesting that the decrease in nicastrin expression may take part in the pathogenesis of ache inversa by influencing the expression of the downstream Notch-HES signaling pathway.