In a three-dimensional reconstructed human epidermis filaggrin-2 is essential for proper cornification.
In a three-dimensional reconstructed human epidermis filaggrin-2 is essential for proper cornification.
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DOI：
10.1038/cddis.2015.29
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发表时间：
2015-02-19
影响因子：
9
通讯作者：
Simon M
中科院分区：
文献类型：
--
作者：
Pendaries V;Le Lamer M;Cau L;Hansmann B;Malaisse J;Kezic S;Serre G;Simon M
特应性皮炎是一种慢性炎症性皮肤病，表皮屏障缺陷。在一组非裔美国儿童中，FLG 2无义突变与该疾病相关。在欧洲患者的表皮中，由FLG 2编码的细丝蛋白相关蛋白细丝蛋白-2的表达降低。为了描述聚丝蛋白-2的功能并评估其缺陷的影响，在三维重建的人表皮（RHE）模型中使用慢病毒介导的shRNA干扰下调其表达。这导致角化不全和致密角质层，角质细胞内存在异常囊泡，RHE表面的pH值升高和游离氨基酸量减少，导致对UVB辐射的敏感性增加。分化标志物的表达略有改变。然而，我们观察到与胱天蛋白酶-14和博来霉素水解酶的量减少平行的角桥蛋白、角蛋白和聚丝蛋白的蛋白水解加工减少。我们的数据表明，聚丝蛋白-2对于适当的角质化和功能性角质层是重要的。其在特应性患者中的下调可能参与疾病相关的表皮损伤。
Atopic dermatitis is a chronic inflammatory skin disease with defects in the epidermal barrier. In a cohort of African-American children, a FLG2 nonsense mutation has been associated with the disease. In the epidermis of European patients, the expression of filaggrin-2, the filaggrin-related protein encoded by FLG2, is decreased. To describe the function of filaggrin-2 and evaluate the impact of its deficiency, its expression was downregulated using lentivirus-mediated shRNA interference in a three-dimensional reconstructed human epidermis (RHE) model. This resulted in parakeratosis and a compact stratum corneum, presence of abnormal vesicles inside the corneocytes, increased pH and reduced amounts of free amino acids at the RHE surface, leading to increased sensitivity to UVB radiations. The expression of differentiation markers was slightly modified. However, we observed reduced proteolytic processing of corneodesmosin, hornerin and filaggrin in parallel with reduced amounts of caspase-14 and bleomycin hydrolase. Our data demonstrated that filaggrin-2 is important for a proper cornification and a functional stratum corneum. Its downregulation in atopic patients may be involved in the disease-associated epidermis impairment.