Knockdown of sodium channel Na x reduces dermatitis symptoms in rabbit skin

• Published in: Laboratory investigation 2020-05, Vol.100 (5), p.751
• Main Authors: Zhao, Jingling, Jia, Shengxian, Xie, Ping, Friedrich, Emily, Galiano, Robert D, Qi, Shaohai, Mao, Renxiang, Mustoe, Thomas A, Hong, Seok Jong
• Format: Article
• Language: English
• Subjects: Animals; Cell Proliferation - genetics; Dermatitis, Atopic - genetics; Dermatitis, Atopic - pathology; Dermatitis, Atopic - physiopathology; Down-Regulation - genetics; Eosinophils - metabolism; Female; Gene Knockdown Techniques; Inflammation - genetics; Inflammation - pathology; Inflammation - physiopathology; Keratinocytes - metabolism; Keratosis - genetics; Keratosis - pathology; Keratosis - physiopathology; Mast Cells - metabolism; Rabbits; Skin - cytology; Skin - pathology; Skin - physiopathology; Voltage-Gated Sodium Channels - genetics; Voltage-Gated Sodium Channels - metabolism
• ISSN: 1530-0307
• DOI: 10.1038/s41374-020-0371-1

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 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 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 knockdown. Upregulation of PAR-2 and thymic stromal lymphopoietin (TSLP), which induce Th2-mediated allergic responses, was inhibited by Na knockdown. In addition, expression of COX-2, IL-1β, IL-8, and S100A9, which are downstream genes of Na and are involved in dermatitis pathogenesis, were also decreased by Na knockdown. Our data show that knockdown of Na relieved dermatitis symptoms in vivo and indicate that Na is a novel therapeutic target for dermatitis, which currently has limited therapeutic options.