Knockdown of sodium channel Nax reduces dermatitis symptoms in rabbit skin

Jingling Zhao, Shengxian Jia, Ping Xie, Emily Friedrich, Robert D. Galiano, Shaohai Qi, Renxiang Mao, Thomas A. Mustoe*, Seok Jong Hong

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

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

Original languageEnglish (US)
Pages (from-to)751-761
Number of pages11
JournalLaboratory Investigation
Volume100
Issue number5
DOIs
StatePublished - May 1 2020

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Zhao, J., Jia, S., Xie, P., Friedrich, E., Galiano, R. D., Qi, S., Mao, R., Mustoe, T. A., & Hong, S. J. (2020). Knockdown of sodium channel Nax reduces dermatitis symptoms in rabbit skin. Laboratory Investigation, 100(5), 751-761. https://doi.org/10.1038/s41374-020-0371-1