Decreased interaction between ZO-1 and occludin is involved in alteration of tight junctions in transplanted epiphora submandibular glands.
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.
Center for Salivary Gland Diseases and Center Laboratory, Peking University School and Hospital of Stomatology, Beijing, 100081, People's Republic of China.
Chong
C
Ding
Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, and Beijing Key Laboratory of Cardiovascular Receptors Research, 38 Xueyuan Road, Haidian District, Beijing, 100191, People's Republic of China.
Xin
X
Cong
Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Street, Haidian District, Beijing, 100081, People's Republic of China.
Xue-Ming
XM
Zhang
Center for Salivary Gland Diseases and Center Laboratory, Peking University School and Hospital of Stomatology, Beijing, 100081, People's Republic of China.
Sheng-Lin
SL
Li
Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, and Beijing Key Laboratory of Cardiovascular Receptors Research, 38 Xueyuan Road, Haidian District, Beijing, 100191, People's Republic of China. pathophy@bjmu.edu.cn.
Li-Ling
LL
Wu
Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Street, Haidian District, Beijing, 100081, People's Republic of China. gyyu@263.net.
Guang-Yan
GY
Yu
D000328:Adult; D047390:Casein Kinase II / Q000378:metabolism; D005260:Female; D006801:Humans; D007766:Lacrimal Apparatus Diseases / Q000209:etiology; D008297:Male; D008875:Middle Aged; D062793:Occludin / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism; D013363:Submandibular Gland / Q000473:pathology / Q000637:transplantation*; D019108:Tight Junctions / Q000378:metabolism*; D055815:Young Adult; D062826:Zonula Occludens-1 Protein / Q000378:metabolism*
D062793:Occludin; D011976:Receptors, Muscarinic; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D047390:Casein Kinase II
Casein kinase 2; Epiphora; Submandibular gland; Tight junction; Transplantation