[P3-2-24] Modulation of O-GlcNAcylation in salivary gland development
Keywords:Acinar cell differentiation、O-GlcNacylation、ER stress
In this study, the developmental role of O-GlcNAcylation, a post-translational modification of intracellular proteins and reported to be involved in various cellular processes including cell cycle progression, signaling, transcription, and stress response, was investigated during salivary gland formation using a range of experimental tools. Immunohistochemical examination of O-GlcNAc Transferase (OGT) and O-GlcNAc during different stages of embryonic and postnatal salivary gland development indicated the potential involvement of O-GlcNAcylation in salivary gland (specifically acinar cell) differentiation. To define its precise roles, we inhibited OGT using a small OGT inhibitor called OSMI-1 during in vitro cultivation of embryonic salivary glands at E14. Following OGT inhibition, we assessed morphological and molecular changes using histology, immunohistochemistry, and real-time quantitative polymerase chain reaction. Overall, the inhibition of OGT led to a delay in terminal bud development and differentiation. Additionally, the predominant localization of ER stress markers (GRP78, HRD1, and IRE1) in the developing buds indicated the induction of ER stress after OSMI-1 treatment, which subsequently resulted in increased apoptosis. Moreover, the treatment with OSMI-1 significantly affected the localization patterns of signaling molecules associated with acinar cell differentiation, including E-cadherin, Vimentin, and Mist1. In summary, our findings provide evidence that O-GlcNAcylation, mediated by OGT, plays a critical role in the development and differentiation of salivary glands.