Mellas Rachel E, Leigh Noel J, Nelson Joel W, McCall Andrew D, Baker Olga J
School of Dentistry, The University of Utah, Salt Lake City, UT, USA (REM, NJL, JWN, OJB)
Department of Oral Biology, University at Buffalo, The State University of New York, Buffalo, NY, USA (ADM)
J Histochem Cytochem. 2015 Jan;63(1):45-56. doi: 10.1369/0022155414555145. Epub 2014 Sep 23.
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.
干燥综合征(SS)是一种慢性炎症性自身免疫性疾病,可导致唾液腺分泌功能障碍,进而引起口干。先前的研究报道,在患有SS的人类小唾液腺中,紧密连接(TJ)蛋白下调且极性丧失,这表明SS患者的TJ结构受到破坏。在本文中,我们使用了NOD/ShiLtJ小鼠,主要目的是评估该模型在未来TJ研究中的适用性。我们发现,在患有SS的小鼠和人类唾液腺中,淋巴细胞浸润近端和远端区域的顶端蛋白组织保持完整。这些区域与对照腺体(即无淋巴细胞浸润)看起来相当。在与唾液上皮丧失一致的淋巴细胞浸润区域,未检测到TJ染色。基因表达研究表明,与年龄匹配的C57BL/6对照相比,20周龄的NOD/ShiLtJ小鼠中大多数TJ没有明显改变。蛋白质表达研究显示,TJ蛋白闭锁小带蛋白-1(ZO-1)、闭合蛋白、紧密连接蛋白-12以及E-钙黏蛋白在NOD/ShiLtJ小鼠中没有显著变化。我们的结果表明,在无淋巴细胞浸润的区域,ZO-1、闭合蛋白和E-钙黏蛋白没有改变。然而,未来有必要对这些结果的功能方面进行测试。