{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:17:49Z","timestamp":1755217069847,"version":"3.43.0"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T00:00:00Z","timestamp":1754352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Dent. Med."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Accordingly, archived biopsy specimens of subjects with a diagnosis of mucocele (control; <jats:italic>n<\/jats:italic>\u2009=\u20097) and those of subjects complaining of dry mouth (experimental; <jats:italic>n<\/jats:italic>\u2009=\u200912) were subjected to histopathological and immunohistochemical assessments for SGK-1, its phosphorylated (active) form (pSGK-1), and the alpha subunit of ENaC (\u03b1-ENaC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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 \u03b1-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 \u03b1-ENaC and SGK-1, but not pSGK-1, for experimental compared to control cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Collectively, the data suggest a difference between the active form of the kinase and \u03b1-ENaC in minor salivary glands in xerostomia and that higher SGK-1 and \u03b1-ENaC may serve as diagnostic markers for this condition.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fdmed.2025.1585554","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T05:25:07Z","timestamp":1754371507000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Expression profiles of SGK-1 and \u03b1-ENaC in minor salivary glands of subjects with xerostomia"],"prefix":"10.3389","volume":"6","author":[{"given":"Mahmood S.","family":"Mozaffari","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafik","family":"Abdelsayed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1067\/mpr.2001.113778","article-title":"A review of saliva: normal composition, flow, and function","volume":"85","author":"Humphrey","year":"2001","journal-title":"J Prosthet Dent"},{"key":"B2","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1111\/prd.12116","article-title":"The physiology of salivary secretion","volume":"70","author":"Proctor","year":"2016","journal-title":"Periodontol 2000"},{"key":"B3","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.gene.2015.12.061","article-title":"Epithelial sodium channel (ENaC) family: phylogeny, structure-function, tissue distribution, and associated inherited diseases","volume":"579","author":"Hanukoglu","year":"2016","journal-title":"Gene"},{"key":"B4","doi-asserted-by":"publisher","first-page":"7775","DOI":"10.3390\/ijms24097775","article-title":"The epithelial sodium channel\u2014an underestimated drug target","volume":"24","author":"Lemmens-Gruber","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1097\/01.asn.0000061777.67332.77","article-title":"Mineralocorticoid effects in the kidney: correlation between alphaENaC, GILZ, and Sgk-1 mRNA expression and urinary excretion of Na+ and K+","volume":"14","author":"Muller","year":"2003","journal-title":"J Am Soc Nephrol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"32074","DOI":"10.1074\/jbc.M111.278283","article-title":"Epithelial sodium channel regulation by cell surface-associated serum- and glucocorticoid-regulated kinase 1","volume":"286","author":"Thomas","year":"2011","journal-title":"J Biol Chem"},{"key":"B7","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1085\/jgp.200409120","article-title":"Mechanisms of regulation of epithelial sodium channel by SGK1 in A6 cells","volume":"124","author":"Alvarez de la Rosa","year":"2004","journal-title":"J Gen Physiol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"3117","DOI":"10.3390\/diagnostics13193117","article-title":"Diagnostic value of labial minor salivary gland biopsy: histological findings of a large Sicca cohort and clinical associations","volume":"13","author":"Triantafyllias","year":"2023","journal-title":"Diagnostics (Basel)"},{"key":"B9","doi-asserted-by":"publisher","first-page":"675288","DOI":"10.3389\/froh.2021.675288","article-title":"Expression profiles of GILZ and SGK-1 in potentially malignant and malignant human oral lesions","volume":"2","author":"Mozaffari","year":"2021","journal-title":"Front Oral Health"},{"key":"B10","doi-asserted-by":"publisher","first-page":"522","DOI":"10.3181\/0806-RM-209","article-title":"Regulation of epithelial Na+ channel (ENaC) in the salivary cell line SMG-C6","volume":"234","author":"Vasquez","year":"2009","journal-title":"Exp Biol Med (Maywood)"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e3465","DOI":"10.21769\/BioProtoc.3465","article-title":"Semi-quantitative determination of protein expression using immunohistochemistry staining and analysis: an integrated protocol","volume":"9","author":"Crowe","year":"2019","journal-title":"Bio Protoc"},{"key":"B12","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH image to ImageJ: 25 years of image analysis","volume":"7","author":"Schneider","year":"2012","journal-title":"Nat Methods"},{"key":"B13","doi-asserted-by":"publisher","first-page":"e39340","DOI":"10.7554\/eLife.39340","article-title":"Structure of the human epithelial sodium channel by cryo-electron microscopy","volume":"7","author":"Noreng","year":"2018","journal-title":"Elife"},{"key":"B14","doi-asserted-by":"publisher","first-page":"H487","DOI":"10.1152\/ajpheart.00800.2020","article-title":"The \u03b4 subunit of epithelial sodium channel in humans\u2014a potential player in vascular physiology","volume":"320","author":"Paudel","year":"2021","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/367463a0","article-title":"Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits","volume":"367","author":"Canessa","year":"1994","journal-title":"Nature"},{"key":"B16","doi-asserted-by":"publisher","first-page":"C447","DOI":"10.1152\/ajpcell.00385.2002","article-title":"The gamma-subunit of ENaC is more important for channel surface expression than the beta-subunit","volume":"284","author":"Konstas","year":"2003","journal-title":"Am J Physiol Cell Physiol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1172\/JCI7869","article-title":"Liddle\u2019s syndrome mutations disrupt cAMP-mediated translocation of the epithelial Na(+) channel to the cell surface","volume":"105","author":"Snyder","year":"2000","journal-title":"J Clin Invest"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1111\/j.1600-0854.2007.00602.x","article-title":"The PY motif of ENaC, mutated in Liddle syndrome, regulates channel internalization, sorting and mobilization from subapical pool","volume":"8","author":"Lu","year":"2007","journal-title":"Traffic"},{"key":"B19","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1161\/HYPERTENSIONAHA.120.14481","article-title":"Epithelial sodium channel and salt-sensitive hypertension","volume":"77","author":"Mutchler","year":"2021","journal-title":"Hypertension"},{"key":"B20","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.archoralbio.2010.09.006","article-title":"Epithelial Na+ channel (ENaC) expression in obstructive sialadenitis of the submandibular gland","volume":"56","author":"Jung","year":"2011","journal-title":"Arch Oral Biol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"30","DOI":"10.55563\/clinexprheumatol\/h9hivf","article-title":"Parotid salivary sodium levels of Sj\u00f6gren\u2019s syndrome patients suggest B-cell mediated epithelial sodium channel disruption","volume":"39","author":"Pringle","year":"2021","journal-title":"Clin Exp Rheumatol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1007\/s00424-005-0026-5","article-title":"Stimulation of the epithelial sodium channel (ENaC) by the serum- and glucocorticoid-inducible kinase (Sgk) involves the PY motifs of the channel but is independent of sodium feedback inhibition","volume":"452","author":"Rauh","year":"2006","journal-title":"Pflugers Arch"},{"key":"B23","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1002\/jcp.30505","article-title":"Detrimental or beneficial: role of endothelial ENaC in vascular function","volume":"237","author":"Zhang","year":"2022","journal-title":"J Cell Physiol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1111\/eos.12536","article-title":"Current concepts on Sj\u00f6gren\u2019s syndrome\u2014classification criteria and biomarkers","volume":"126","author":"Jonsson","year":"2018","journal-title":"Eur J Oral Sci"},{"key":"B25","doi-asserted-by":"publisher","first-page":"12903","DOI":"10.3390\/ijms222312903","article-title":"Salivary biomarkers in patients with Sj\u00f6gren\u2019s syndrome\u2014a systematic review","volume":"22","author":"Jung","year":"2021","journal-title":"Int J Mol Sci"}],"container-title":["Frontiers in Dental Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fdmed.2025.1585554\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T05:25:08Z","timestamp":1754371508000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fdmed.2025.1585554\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,5]]},"references-count":25,"alternative-id":["10.3389\/fdmed.2025.1585554"],"URL":"https:\/\/doi.org\/10.3389\/fdmed.2025.1585554","relation":{},"ISSN":["2673-4915"],"issn-type":[{"type":"electronic","value":"2673-4915"}],"subject":[],"published":{"date-parts":[[2025,8,5]]},"article-number":"1585554"}}