Mechanisms of salivary gland cell proliferation in vitro by P2Y2R activation
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Sjögren's syndrome (SS) and the side-effects of γ-radiation therapies for head and neck cancers cause salivary gland dysfunction. Salivary gland regeneration has been considered to be a very promising approach for restoring saliva secretion. To regenerate a functional salivary gland in a clinical setting, it is first necessary to gain a better understanding of the mechanisms involved in salivary gland regeneration. This thesis focuses on the proliferative role of extracellular nucleotides via the activation of the P2Y2 nucleotide receptor in salivary gland epithelial cells. Our previous studies have shown that the P2Y2R interacts with many signaling molecules to regulate multiple signaling pathways involved in cell proliferation. These studies support the overall hypothesis that expression and activation of P2Y2Rs in damaged or diseased salivary gland cells promotes cell proliferation. In this project, we demonstrate that activation of the P2Y2R increases the proliferation of human salivary gland (HSG) epithelial cells in vitro. Other data indicate that inhibition of Src and ERK1/2 prevents P2Y2R-mediated proliferation of HSG cells. Thus, the current results suggest that activation of P2Y2Rs by extracellular nucleotides promotes proliferation of HSG cells by stimulating Src-dependent pathway and activating ERK1/2. Accordingly, the P2Y2R represents a promising target for salivary gland regeneration.