Inhibition of Src and p38 MAP kinases suppresses the change of claudin expression induced on dedifferentiation of primary cultured parotid acinar cells.
نویسندگان
چکیده
Sjögren's syndrome and therapeutic radiation for head and neck cancers result in irreversible changes in the parenchyma of salivary glands, loss of acinar cells, prominence of duct cells, and fibrosis. To clarify mechanisms of salivary gland dysfunction, we identified a signaling pathway involved in the dedifferentiation of primary cultures of parotid acinar cells. We reported previously that the expression pattern of claudins changes during culture, is related to the three-dimensional organization of the cells, and reflects their ability to function as acinar cells. In this study, we found that this change of claudin expression is a process of dedifferentiation, because expression of other differentiation markers also changes during culture. The expression levels of claudins-4 and -6, cytokeratin 14, and vimentin are increased, and those of claudin-10, aquaporin 5, and amylase are decreased. Inhibitors of Src and p38 MAP kinases suppress these changes and increase the expression of acinar marker proteins. Differences in extracellular matrix components have no effect. Activation of p38 MAP kinase occurs during cell isolation from the parotid glands and is retained up to 6 h after the isolation. In contrast, activation of Src kinases does not increase during the cell isolation. The Src inhibitor PP1 suppresses the activation of p38 MAP kinase. Therefore, cellular stresses induced during cell isolation cause dedifferentiation and transition to duct-like cells through activation of p38 MAP kinase and constitutively active Src kinases.
منابع مشابه
Inhibition of Src and p38 MAP Kinases Suppresses the Change of Claudin Expression Induced upon Dedifferentiation of Primary Cultured Parotid Acinar Cells
متن کامل
Parotid acinar cells transiently change to duct-like cells during epithelial-mesenchymal transition.
Hyposecretion of saliva and consequent dry mouth lead to severe caries and periodontal disease. Therapeutic radiation for head and neck cancer and sialadenitis result in atrophy and fibrosis of salivary glands, but the mechanism is not clear. As a model for dysfunction of salivary glands, we examined the change of gene expression patterns in primary cultured parotid acinar cells. The expression...
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ورودعنوان ژورنال:
- American journal of physiology. Cell physiology
دوره 294 3 شماره
صفحات -
تاریخ انتشار 2008