title: Expression of epithelial sodium channel (ENaC) and CFTR in the human epidermis and epidermal appendages.
abstract: A major function of the skin is the regulation of body temperature by sweat secretions. Sweat glands secrete water and salt, especially NaCl. Excreted water evaporates, cooling the skin surface, and Na+ions are reabsorbed by the epithelial sodium channels (ENaC). Mutations in ENaC subunit genes lead to a severe multi-system (systemic) form of pseudohypoaldosteronism (PHA) type I, characterized by salt loss from aldosterone target organs, including sweat glands in the skin. In this study, we mapped the sites of localization of ENaC in the human skin by confocal microscopy using polyclonal antibodies generated against human αENaC. Our results reveal that ENaC is expressed strongly in all epidermal layers except stratum corneum, and also in the sebaceous glands, eccrine glands, arrector pili smooth muscle cells, and intra-dermal adipocytes. In smooth muscle cells and adipocytes, ENaC is co-localized with F-actin. No expression of ENaC was detected in the dermis. CFTR is strongly expressed in sebaceous glands. In epidermal appendages noted, except the eccrine sweat glands, ENaC is mainly located in the cytoplasm. In the eccrine glands and ducts, ENaC and CFTR are located on the apical side of the membrane. This localization of ENaC is compatible with ENaC's role in salt reabsorption. PHA patients may develop folliculitis, miliaria rubra, and atopic dermatitis-like skin lesions, due to sweat gland duct occlusion and inflammation of eccrine glands as a result of salt accumulation.
authors.affiliation: Laboratory of Cell Biology, Ariel University, Ariel, 40700, Israel. mbiochem@gmail.com.
authors.forename: Israel
authors.identifier: http://orcid.org/0000-0003-3889-0320
authors.initials: I
authors.lastname: Hanukoglu
authors.affiliation: Laboratory of Cell Biology, Ariel University, Ariel, 40700, Israel.|Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.
authors.forename: Vijay R
authors.initials: VR
authors.lastname: Boggula
authors.affiliation: Division of Pathology, E. Wolfson Medical Center, Holon, Israel.
authors.forename: Hananya
authors.initials: H
authors.lastname: Vaknine
authors.affiliation: Laboratory of Cell Biology, Ariel University, Ariel, 40700, Israel.
authors.forename: Sachin
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.|Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA.|Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kleyman
authors.affiliation: Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.|Division of Pediatric Endocrinology, E. Wolfson Medical Center, Holon, Israel.
authors.forename: Aaron
authors.identifier: http://orcid.org/0000-0003-1486-6641
authors.initials: A
authors.lastname: Hanukoglu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism*; D053503:Epithelial Sodium Channels / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D053503:Epithelial Sodium Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: Actin; Eccrine gland; Epidermis; Keratinocytes; Pseudohypoaldosteronism; Renin–angiotensin–aldosterone system; Smooth muscle cells; Sweat glands