The skin plays a critical role in maintenance of water homeostasis. Dysfunction of the skin barrier causes not only delayed wound healing and hypertrophic scarring, but it also contributes to the development of various skin diseases. Dermatitis is a chronic inflammatory skin disorder that has several different subtypes. Skin of contact dermatitis and atopic dermatitis (AD) show epidermal barrier dysfunction. Na_x is a sodium channel that regulates inflammatory gene expression in response to perturbation of barrier function of the skin. We found that in vivo knockdown of Na_x using RNAi reduced hyperkeratosis and keratinocyte hyperproliferation in rabbit ear dermatitic skin. Increased infiltration of inflammatory cells (mast cells, eosinophils, T cells, and macrophages), a characteristic of dermatitis, was reduced by Na_x knockdown. Upregulation of PAR-2 and thymic stromal lymphopoietin (TSLP), which induce Th2-mediated allergic responses, was inhibited by Na_x knockdown. In addition, expression of COX-2, IL-1β, IL-8, and S100A9, which are downstream genes of Na_x and are involved in dermatitis pathogenesis, were also decreased by Na_x knockdown. Our data show that knockdown of Na_x relieved dermatitis symptoms in vivo and indicate that Na_x is a novel therapeutic target for dermatitis, which currently has limited therapeutic options.

皮肤在维持水分稳态方面起着至关重要的作用。皮肤屏障功能障碍不仅会导致伤口愈合延迟和增生性瘢痕形成，还会导致各种皮肤病的发展。皮炎是一种慢性炎症性皮肤病，有几种不同的亚型。接触性皮炎和特应性皮炎（AD）的皮肤表现为表皮屏障功能障碍。Na _x是调节炎症基因表达以响应皮肤屏障功能扰动的钠通道。_{我们发现 Na x}的体内敲低使用 RNAi 可减少兔耳皮炎皮肤的角化过度和角质形成细胞过度增殖。炎症细胞（肥大细胞、嗜酸性粒细胞、T 细胞和巨噬细胞）的浸润增加是皮炎的一个特征，Na _x敲低可减少这种浸润。诱导 Th2 介导的过敏反应的 PAR-2 和胸腺基质淋巴细胞生成素 (TSLP) 的上调受到 Na _x敲低的抑制。此外，Na x 的下游基因 COX-2、IL-1β、IL-8 和 S100A9 的表达也参与了_皮炎发病机制，Na _x的敲低也降低了它们。我们的数据表明，Na _x的敲低可缓解体内皮炎症状，并表明 Na _x是皮炎的新型治疗靶点，目前治疗选择有限。