Mastication Regulates Nitrate Homeostasis Through Lipid Raft-Mediated Sialin Translocation

To investigate the role of mastication on the salivary nitrate transport and elucidate the underlying mechanisms.

Systemic nitrate levels were clinically compared between individuals with masticatory dysfunction and healthy individuals. Behavioral assessments were performed in mice with reduced masticatory activity to examine the impact on anxiety-like behavior. Mechanical stimulation was applied to salivary gland epithelial cells and tissues to explore the expression, localization, and translocation mechanisms of Sialin, a nitrate transporter encoded by the Slc17a5.

Individuals with impaired mastication exhibited significantly lower systemic nitrate levels compared to healthy controls. In mice, decreased masticatory activity was associated with increased anxiety-like behavior. In vitro, mechanical force stimulated the upregulation and apical translocation of Sialin in human salivary gland epithelial cells (HSGs). Sialin was predominantly localized within lipid rafts, and its force-induced translocation was mediated by activation of the Piezo1 channel, which facilitated the movement of lipid rafts to the apical membrane, thereby enhancing nitrate secretion.

Mastication sustains nitrate homeostasis and mitigates anxiety-like behavior in mice by mechanically activating the Piezo1 channel, thus facilitating the lipid raft-mediated translocation of Sialin to the apical membrane in salivary gland cells.