Research ArticleSKIN DISEASE

Sodium channel Nax is a regulator in epithelial sodium homeostasis

Science Translational Medicine  04 Nov 2015:
Vol. 7, Issue 312, pp. 312ra177
DOI: 10.1126/scitranslmed.aad0286

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Rubbing sodium in a wound

The skin serves as a critical barrier to the outside world; however, little is known about how this barrier returns to homeostasis after it is disturbed. Water loss occurs during many skin disorders, resulting in an increase in extracellular sodium concentration. Now, Xu et al. report that the sodium channel Nax functions as a sodium sensor that contributes to epithelial homeostasis. Nax, which is present in multiple epithelial tissues and up-regulated in scars, increases sodium flux and induces the downstream production of mediators of epithelial cell proliferation and inflammation that may lead to scar formation. Indeed, blocking Nax in animal models decreases scarring and atopic dermatitis–like symptoms, suggesting that Nax may contribute to epithelial homeostasis.

Abstract

The mechanisms by which the epidermis responds to disturbances in barrier function and restores homeostasis are unknown. With a perturbation of the epidermal barrier, water is lost, resulting in an increase in extracellular sodium concentration. We demonstrate that the sodium channel Nax functions as a sodium sensor. With increased extracellular sodium, Nax up-regulates prostasin, which results in activation of the sodium channel ENaC, resulting in increased sodium flux and increased downstream mRNA synthesis of inflammatory mediators. Nax is present in multiple epithelial tissues, and up-regulation of its downstream genes is found in hypertrophic scars. In animal models, blocking Nax expression results in improvement in scarring and atopic dermatitis–like symptoms, both of which are pathological conditions characterized by perturbations in barrier function. These findings support an important role for Nax in maintaining epithelial homeostasis.

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