Cerutis, D. R.; Kumar, D.; Nichols, M. G.; Roemer, G. R.; Fluent, M. E.; Miyamoto, T.; Alnouti, Y.

This study builds on our previous findings on the role of salivary lysophosphatidic acid (LPA) species in humans to investigate their presence, together with salivary gland LPA receptor (LPAR) expression in a Porphyromonas gingivalis- infected murine (C57BL/6J) model of periodontal disease (PD). Utilizing LC-MS/MS for LPA analysis alongside confocal LPAR imaging and second harmonic (SHG) imaging for collagen visualization, we compared mouse salivary LPA levels and gland LPAR expression to previously established human and mouse data. The findings reveal that while healthy mouse saliva maintains low homeostatic LPA levels, PD triggers an ~ 10-fold increase, mirroring the elevation we observed in PD patients. Furthermore, the study confirmed the presence of LPA1, LPA3, and LPA4 within submandibular gland (SMG) tissue. Notably, LPA3 was identified as the most widely distributed subtype, while providing the first evidence of LPA4 expression in adult mouse salivary glands. The presence of multiple LPARs suggests that LPA signaling is a critical factor in salivary gland biology. The documented existence of multiple LPARs within salivary glands indicates that they must be taken into consideration in future research concerning autoimmune conditions, and in pharmacological studies involving drugs that impact salivary gland biology and secretory function.