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

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 immunohistochemical study was performed to measure the expressions 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 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 Notch1, Notch3 and HES-1 expressions(r = 0.831, 0.748 and 0.807, 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-HES signaling pathway-associated proteins, suggesting that the decrease in nicastrin expression may take part in the pathogenesis of acne inversa by influencing the expression of the downstream Notch-HES signaling pathway. Key words: Genes; Mutation; Signal transduction; Acne inversa; Nicastrin gene; Notch-HES signaling pathway