ABSTRACT O‐GlcNAcylation is a post‐translational modification involved in various cellular processes, including cell cycle progression, signaling, transcription, and stress response. Mouse salivary gland morphogenesis shows specific localization patterns of O‐GlcNAc transferase (OGT) and O‐GlcNAc in developing acinar cells, suggesting a potential involvement of O‐GlcNAcylation in acinar cell differentiation‐related signaling molecules. To define its underlying mechanisms, this study used an OGT inhibitor, OSMI‐1, and small interfering RNA (siRNA) targeting OGT, during in vitro cultivation of submandibular glands and assessed morphological and molecular alterations using histology, immunohistochemistry, Western blot, and RT‐qPCR. As expected, OGT inhibition impaired terminal bud morphogenesis and altered cellular physiology. OSMI‐1 treatment disrupted acinar cell differentiation, reflected by changes in expression patterns of signaling molecules crucial to acinar cell differentiation, including Sox9, Sox10, E‐cadherin, and Mist1. Altered expression patterns of cytokeratins, including CK14 and CK18, confirmed altered ductal morphology. Therefore, our findings highlight the essential role of OGT‐mediated O‐GlcNAcylation in salivary gland morphogenesis with post‐translational regulation of key signaling molecules governing functional differentiation of acinar cells.
Pokharel et al. (Thu,) studied this question.