TY - JOUR
T1 - Sodium channel Nax is a regulator in epithelial sodium homeostasis
AU - Xu, Wei
AU - Hong, Seok Jong
AU - Zhong, Aimei
AU - Xie, Ping
AU - Jia, Shengxian
AU - Xie, Zhong
AU - Zeitchek, Michael
AU - Niknam-Bienia, Solmaz
AU - Zhao, Jingling
AU - Porterfield, D. Marshall
AU - Surmeier, D. James
AU - Leung, Kai P.
AU - Galiano, Robert D.
AU - Mustoe, Thomas A.
PY - 2015/11/4
Y1 - 2015/11/4
N2 - 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.
AB - 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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U2 - 10.1126/scitranslmed.aad0286
DO - 10.1126/scitranslmed.aad0286
M3 - Article
C2 - 26537257
AN - SCOPUS:84946800588
SN - 1946-6234
VL - 7
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 312
M1 - 312ra177
ER -