Zonula Occludens-1, Occludin and E-cadherin Expression and Organization in Salivary Glands with Sjögren’s Syndrome

Abstract

Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disorder that causes secretory dysfunction of the salivary glands leading to dry mouth. Previous studies reported that tight junction (TJ) proteins are down-regulated and lose polarity in human minor salivary glands with SS, suggesting that TJ structure is compromised in SS patients. In this paper, we utilized the NOD/ShiLtJ mouse with the main goal of evaluating this model for future TJ research. We found that the organization of apical proteins in areas proximal and distal to lymphocytic infiltration remained intact in mouse and human salivary glands with SS. These areas looked comparable to control glands (i.e., with no lymphocytic infiltration). TJ staining was absent in areas of lymphocytic infiltration coinciding with the loss of salivary epithelium. Gene expression studies show that most TJs are not significantly altered in 20-week-old NOD/ShiLtJ mice as compared with age-matched C57BL/6 controls. Protein expression studies revealed that the TJ proteins, zonula occludens-1 (ZO-1), occludin, claudin-12, as well as E-cadherin, do not significantly change in NOD/ShiLtJ mice. Our results suggest that ZO-1, occludin and E-cadherin are not altered in areas without lymphocytic infiltration. However, future studies will be necessary to test the functional aspect of these results.

Changes in the Submandibular Salivary Gland Epithelial Cell Subpopulations During Progression of Sjögren's Syndrome‐Like Disease in the NOD/ShiLtJ Mouse Model

“…However, upon closer investigation we found that the tissue architecture up to 22 weeks, as determined by VH&E stains, the ECAD positive epithelial distributions and the Aqp5 + acinar, K7 + ductal, and SM α‐actin + myoepithelial populations were not obviously disrupted, including tissue areas directly adjacent to the lymphocytic infiltrations. Our observations that epithelial architecture is not significantly disrupted in the NOD/ShiLtJ mouse up to 22 weeks of age is consistent with another recent report (Mellas et al, ), and suggests that the presence of the advanced lymphocytic infiltrates may not directly disrupt the epithelium at this stage of disease progression. In the human SS affected tissues, we observed that large areas of the epithelium are disrupted surrounding the focal infiltrates and show an amorphous morphology, consistent with other reports (Goicovich et al, ; Molina et al, ).…”

Current trends in salivary gland tight junctions

“…39 Furthermore, occludin has been shown to be expressed in acini and ducts from human minor salivary and mouse submandibular glands; 14 likewise, this protein has been found in cell lines of salivary gland origin (e.g., in polarized Par-C10 and SMIE cells). 40,91 Finally, mice lacking occludin showed loss of cytoplasmic granules in striated ducts from salivary glands, 92 suggesting that occludin may control salivary gland phenotype in both acinar and ductal structures.…”

“…Interestingly, deficiency of ZO-1 did not exert any effects on the localization of ZO-2/ZO-3 at junctional sites but did induce mislocalization of endothelial JAMs in the yolk sac, 109 which might explain the disturbance of vascular development. ZO-1 is expressed in acini, ducts, and inter-glandular endothelial cells from human major salivary glands and mouse submandibular glands 14,39,81 and is also co-localized with claudin-16 at the excretory duct of human major salivary glands. 81 ZO-1 has been used as a marker for salivary gland polarity and differentiation; 110 however, further studies are needed to determine the molecular mechanisms by which ZO-1 modulates TJs in salivary glands.…”

“…For instance, salivary gland acini allow paracellular flux of water while ducts remain impermeable to water during saliva secretion. 12 In Sj€ ogren's syndrome (SS, an autoimmune disease that causes salivary gland hypofunction), TJ expression and organization are altered, 13,14 indicating that they have a significant role in maintaining intact salivary gland functioning. This review seeks to provide an overview of what is currently known, as well as the major questions and future research directions, regarding tight junction expression, organization and function within salivary glands.…”

Brain‐derived neurotrophic factor preserves intestinal mucosal barrier function and alters gut microbiota in mice

“…ZO‐1 and occludin form a high resistance barrier in the bladder epithelium, and deterioration of these proteins marks the disruption of the pulmonary epithelial barrier [7–10]. Studies report that in human minor salivary glands, as claudin‐1 and claudin‐4 increase, ZO‐1 and occludin decrease [11]. Additionally, the expression of the epithelial tight junction proteins ZO‐1, occludin, claudin‐1 and claudin‐2 can be regulated by brain‐derived neurotrophic factor (BDNF) [12].…”