Abstract
Tight junctions (TJs) in salivary epithelium play an important role in regulating saliva secretion. Autologous transplantation of submandibular glands (SMGs) is an effective method to treat severe dry eye syndrome. However, epiphora occurs in some patients 6 months after transplantation. We previously found that the acinar TJs are enlarged in rabbit SMGs after long-term transplantation, but the exact TJ components involved in the epiphora are still unknown. Here, we found that the mRNA and protein expression of ZO-1 and occludin were increased in the transplanted SMGs obtained from epiphora patients, while other TJs were unchanged. The intensity of ZO-1 and occludin at the apicolateral membranes as well as occludin in the cytoplasm were increased in epiphora SMGs, but the interaction between ZO-1 and occludin was decreased as evidenced by both co-immunoprecipitation assay and co-immunofluorescence staining. Mechanically, the expression of casein kinase 2α (CK2α) and CK2β, which was reported to affect occludin modification and the interaction of occludin with ZO-1 in previous literatures, were increased in epiphora glands. Moreover, activation of muscarinic acetylcholine receptor (mAChR) by carbachol directly decreased the interaction between ZO-1 and occludin and increased the acinar TJ width in the freshly isolated human SMGs, whereas these effects were abolished by pretreatment with CK2 inhibitor. Taken together, our findings suggest that decreased interaction between ZO-1 and occludin might contribute to the epiphora occurred in the transplanted SMGs, and mAChR together with the intracellular molecule CK2 might be responsible for the alteration of TJs in epiphora glands.
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Acknowledgements
This study was supported by the National Natural Science Foundation of China 81200799 (CD), 81300893 (XC) and 81470756 (GYY), and Beijing Natural Science Foundation 7173263 (XC).
Author’s contributions
CD and XC performed the major experiments and wrote the manuscript. XMZ and SLL participated in data interpretation and manuscript improvement. LLW and GYY designed the study, analyzed the data, and wrote the manuscript. All authors read and approved the final manuscript.
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Chong Ding and Xin Cong contributed equally to this work.
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Ding, C., Cong, X., Zhang, XM. et al. Decreased interaction between ZO-1 and occludin is involved in alteration of tight junctions in transplanted epiphora submandibular glands. J Mol Hist 48, 225–234 (2017). https://doi.org/10.1007/s10735-017-9716-5
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DOI: https://doi.org/10.1007/s10735-017-9716-5