IgG4-related sialadenitis (IgG4-RS) is a chronic fibro-inflammatory disease characterized by swelling of salivary glands and varying degrees of xerostomia. Tight junctions (TJs) play an essential role in maintaining secretory function by regulating the paracellular flow of ions and water. However, whether TJs are altered and contribute to the hyposecretion in IgG4-RS is not fully understood. Here, a total of 399 differentially expressed proteins were identified in IgG4-RS submandibular glands (SMGs) and enriched in the regulation of actin cytoskeleton and the salivary secretion. Real-time PCR results showed that the mRNA levels of claudin-3, -4, -6, -7, -8, -10, -12, occludin, and ZO-1 were significantly lower, whereas claudin-1 and -5 were higher in IgG4-RS SMGs. Immunohistochemical and immunofluorescence staining revealed that claudin-1, -3, -4, occludin, and ZO-1 were mainly distributed at apicolateral membranes in acini and ducts of SMGs from controls, whereas claudin-1 protein intensity at apicolateral membrane was elevated, while the staining of claudin-3, -4, and ZO-1 were reduced in IgG4-RS SMGs. Occludin was dispersed into cytoplasm of acini and ducts in SMGs of patients. Among them, claudin-3 and ZO-1 protein levels were positively correlated with saliva flow rate. Furthermore, the decreased fluorescence intensity of F-actin at peri-apicolateral membranes and the loss of ZO-1 staining at the same location were observed in acinar and ductal cells of IgG4-RS SMGs, which might be responsible for disorganization of TJ complex. Taken together, these findings indicate that the integrity of TJ complex of SMGs is impaired and might contribute to hyposalivation of IgG4-RS patients.

中文翻译：

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紧密连接结构的破坏助长了IgG4相关性涎腺炎的分泌功能障碍

IgG4相关性涎腺炎（IgG4-RS）是一种慢性纤维炎性疾病，其特征是唾液腺肿胀和不同程度的口腔干燥症。紧密连接（TJ）通过调节离子和水的细胞旁流动在维持分泌功能中起着至关重要的作用。但是，尚未完全了解TJ是否改变并有助于IgG4-RS的分泌减少。在这里，在IgG4-RS下颌下腺（SMG）中总共鉴定出399种差异表达的蛋白质，并丰富了肌动蛋白细胞骨架的调节和唾液分泌。实时PCR结果显示claudin-3，-4，-6，-7，-8，-10，-12，occludin和ZO-1的mRNA水平显着降低，而claudin-1和-5在IgG4-RS SMG中较高。免疫组织化学和免疫荧光染色显示claudin-1，-3，-4，occludin和ZO-1主要分布在对照的SMGs的腺泡和腺管旁膜上，而apicoside-1膜上的claudin-1蛋白强度升高，而claudin-3，-4和ZO-1的染色减少在IgG4-RS SMG中。Occludin分散在患者SMG的腺泡和导管的细胞质中。其中，claudin-3和ZO-1蛋白水平与唾液流速呈正相关。此外，在IgG4-RS SMGs的腺泡和导管细胞中，在腋旁膜的F-肌动蛋白的荧光强度降低和在同一位置的ZO-1染色消失，这可能是造成TJ复合体紊乱的原因。综上所述，这些发现表明，SMG的TJ复合体的完整性受损，并且可能导致IgG4-RS患者的唾液分泌不足。