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

IntroductionEpithelial 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...

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Main Authors: Mahmood S. Mozaffari, Rafik Abdelsayed
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Dental Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fdmed.2025.1585554/full
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author Mahmood S. Mozaffari
Rafik Abdelsayed
author_facet Mahmood S. Mozaffari
Rafik Abdelsayed
author_sort Mahmood S. Mozaffari
collection DOAJ
description IntroductionEpithelial 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.MethodsAccordingly, 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).ResultsControl 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.DiscussionCollectively, 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.
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spelling doaj-art-4d365c14d9974e80b60aca67c965aa4a2025-08-20T03:43:54ZengFrontiers Media S.A.Frontiers in Dental Medicine2673-49152025-08-01610.3389/fdmed.2025.15855541585554Expression profiles of SGK-1 and α-ENaC in minor salivary glands of subjects with xerostomiaMahmood S. Mozaffari0Rafik Abdelsayed1Department of Oral Biology, The Dental College of Georgia, Augusta University, Augusta, GA, United StatesOral Health and Diagnostic Sciences, The Dental College of Georgia, Augusta University, Augusta, GA, United StatesIntroductionEpithelial 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.MethodsAccordingly, 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).ResultsControl 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.DiscussionCollectively, 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.https://www.frontiersin.org/articles/10.3389/fdmed.2025.1585554/fulllower lip biopsysalivary glandsserum and glucocorticoid-regulated kinase-1epithelial sodium channelxerostomia
spellingShingle Mahmood S. Mozaffari
Rafik Abdelsayed
Expression profiles of SGK-1 and α-ENaC in minor salivary glands of subjects with xerostomia
Frontiers in Dental Medicine
lower lip biopsy
salivary glands
serum and glucocorticoid-regulated kinase-1
epithelial sodium channel
xerostomia
title Expression profiles of SGK-1 and α-ENaC in minor salivary glands of subjects with xerostomia
title_full Expression profiles of SGK-1 and α-ENaC in minor salivary glands of subjects with xerostomia
title_fullStr Expression profiles of SGK-1 and α-ENaC in minor salivary glands of subjects with xerostomia
title_full_unstemmed Expression profiles of SGK-1 and α-ENaC in minor salivary glands of subjects with xerostomia
title_short Expression profiles of SGK-1 and α-ENaC in minor salivary glands of subjects with xerostomia
title_sort expression profiles of sgk 1 and α enac in minor salivary glands of subjects with xerostomia
topic lower lip biopsy
salivary glands
serum and glucocorticoid-regulated kinase-1
epithelial sodium channel
xerostomia
url https://www.frontiersin.org/articles/10.3389/fdmed.2025.1585554/full
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