Expression profiles of SGK-1 and α-ENaC in minor salivary glands of subjects with xerostomia.

Abstract

Introduction: Epithelial sodium channel (ENaC) is a major conduit for sodium transport across the cell membrane, and its activity is regulated by multiple factors/mechanisms, including the serum and glucocorticoid-regulated kinase-1 (SGK-1). Saliva production and secretion are complex processes, with ENaC regulation of the ionic composition of saliva being an essential event prior to the ultimate secretion of hypotonic saliva into the oral cavity. However, the status of salivary gland SGK-1, in the context of ENaC, remains to be determined. We tested the hypothesis that lower lip minor salivary gland expressions of SGK-1 and ENaC are affected in subjects reporting xerostomia.

Methods: Accordingly, archived biopsy specimens of subjects with a diagnosis of mucocele (control; n = 7) and those of subjects complaining of dry mouth (experimental; n = 12) were subjected to histopathological and immunohistochemical assessments for SGK-1, its phosphorylated (active) form (pSGK-1), and the alpha subunit of ENaC (α-ENaC).

Results: Control specimens displayed extravasated mucus surrounded by a capsule of inflamed granulation tissue, while experimental specimens showed patchy periductal, predominantly lymphocytic, infiltrates. Control specimens showed variable degrees of SGK-1 and pSGK-1 immunolabeling of ductal epithelial cells. In contrast, experimental specimens displayed patchy and strong SGK-1 but variable degrees of pSGK-1 immunolabeling of ductal epithelial cells. While control specimens showed variable ductal α-ENaC immunolabeling, those of the experimental group displayed primarily diffuse cytoplasmic, with some membrane, immunolabeling in ductal cells. Semi-quantitative analyses, using ImageJ Fiji, showed increased normalized staining for α-ENaC and SGK-1, but not pSGK-1, for experimental compared to control cases.

Discussion: Collectively, the data suggest a difference between the active form of the kinase and α-ENaC in minor salivary glands in xerostomia and that higher SGK-1 and α-ENaC may serve as diagnostic markers for this condition.