title: Sodium channel Nax is a regulator in epithelial sodium 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.
authors.affiliation: Laboratory for Wound Repair and Regenerative Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Laboratory for Wound Repair and Regenerative Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Seok Jong
authors.initials: SJ
authors.lastname: Hong
authors.affiliation: Laboratory for Wound Repair and Regenerative Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
authors.forename: Aimei
authors.initials: A
authors.lastname: Zhong
authors.affiliation: Laboratory for Wound Repair and Regenerative Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Xie
authors.affiliation: Laboratory for Wound Repair and Regenerative Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Shengxian
authors.initials: S
authors.lastname: Jia
authors.affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Department of Agricultural and Biological Engineering, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Zeitchek
authors.affiliation: Laboratory for Wound Repair and Regenerative Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Solmaz
authors.initials: S
authors.lastname: Niknam-Bienia
authors.affiliation: Laboratory for Wound Repair and Regenerative Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Department of Burns, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Jingling
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Agricultural and Biological Engineering, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: D Marshall
authors.initials: DM
authors.lastname: Porterfield
authors.affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: D James
authors.initials: DJ
authors.lastname: Surmeier
authors.affiliation: Microbiology Branch, U.S. Army Dental and Trauma Research Detachment, Institute of Surgical Research, JB Fort Sam Houston, San Antonio, TX 78234, USA.
authors.forename: Kai P
authors.initials: KP
authors.lastname: Leung
authors.affiliation: Laboratory for Wound Repair and Regenerative Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Galiano
authors.affiliation: Laboratory for Wound Repair and Regenerative Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. tmustoe@nm.org.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Mustoe
mesh_terms: D000818:Animals; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology; D003876:Dermatitis, Atopic / Q000378:metabolism / Q000473:pathology; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D015640:Ion Channel Gating; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D008812:Mice, Hairless; D011817:Rabbits; D012697:Serine Endopeptidases / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D015854:Up-Regulation; D014982:Xenopus laevis; D000099271:Prostasin
chemical_list: D053503:Epithelial Sodium Channels; D012697:Serine Endopeptidases; D012964:Sodium; D000099271:Prostasin