Mozaffari Mahmood S, Abdelsayed Rafik
Department of Oral Biology, The Dental College of Georgia, Augusta University, Augusta, GA, United States.
Oral Health and Diagnostic Sciences, The Dental College of Georgia, Augusta University, Augusta, GA, United States.
Front Dent Med. 2025 Aug 5;6:1585554. doi: 10.3389/fdmed.2025.1585554. eCollection 2025.
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.
Accordingly, archived biopsy specimens of subjects with a diagnosis of mucocele (control; = 7) and those of subjects complaining of dry mouth (experimental; = 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).
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.
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.
上皮钠通道（ENaC）是钠离子跨细胞膜转运的主要途径，其活性受多种因素/机制调节，包括血清和糖皮质激素调节激酶-1（SGK-1）。唾液的产生和分泌是复杂的过程，ENaC对唾液离子组成的调节是低渗唾液最终分泌到口腔之前的一个重要事件。然而，在ENaC背景下唾液腺SGK-1的状态仍有待确定。我们检验了这样一个假设，即报告有口干症状的受试者下唇小唾液腺中SGK-1和ENaC的表达受到影响。
相应地，对诊断为黏液囊肿的受试者（对照组；n = 7）和主诉口干的受试者（实验组；n = 12）的存档活检标本进行组织病理学和免疫组织化学评估，检测SGK-1、其磷酸化（活性）形式（pSGK-1）和ENaC的α亚基（α-ENaC）。
对照标本显示有外渗的黏液，周围是炎症性肉芽组织包膜，而实验标本显示导管周围散在的、主要为淋巴细胞的浸润。对照标本显示导管上皮细胞有不同程度的SGK-1和pSGK-1免疫标记。相比之下，实验标本显示导管上皮细胞有散在且强烈的SGK-1免疫标记，但pSGK-1免疫标记程度不同。对照标本显示导管α-ENaC免疫标记程度不同，而实验组标本主要显示导管细胞中有弥漫性细胞质免疫标记，部分有膜免疫标记。使用ImageJ Fiji进行的半定量分析显示，与对照病例相比，实验组α-ENaC和SGK-1的标准化染色增加，但pSGK-1没有增加。
总体而言，数据表明口干患者小唾液腺中激酶的活性形式与α-ENaC之间存在差异，较高的SGK-1和α-ENaC可能作为这种情况的诊断标志物。
