Salivary Gland Function and Hyposalivation Management

Salivary glands are exocrine organs that secrete a complex fluid essential for oral homeostasis, initial digestion and mucosal defence. Acinar cells produce a seromucous secretion rich in enzymes, mucins and antimicrobial factors, while ductal cells modify ionic content and pH. Myoepithelial cells support acinar contraction and aid saliva expulsion. Hyposalivation, defined by reduced salivary flow, often manifests as xerostomia (the subjective feeling of dry mouth) and is provoked by ageing, systemic disease, radiotherapy and medication. Persistent hyposalivation compromises mastication, taste, speech and tooth integrity, and predisposes to infection. Management spans diagnostic assessment of unstimulated and stimulated flow rates, symptomatic relief with sialogogues and saliva substitutes, and emerging regenerative and cell-based approaches aimed at restoring glandular architecture and function.

Research from Nature Portfolio

Recent studies employing single-cell RNA sequencing and conditional gene deletion have illuminated the pivotal role of fibroblast growth factor receptor 2 (FGFR2) in seromucous acinar differentiation. Signalling via FGFR2 and downstream MAPK pathways governs secretory gene expression, and mesenchyme-derived FGF7 orchestrates acinar maturation. This work provides a molecular rationale for targeted regenerative strategies to replenish dysfunctional acini.

As a proof of concept for whole-organ replacement, bioengineering of a salivary gland germ has demonstrated full morphogenesis and functional integration upon orthotopic transplantation. The engineered organ recapitulates acinar and ductal compartments with appropriate innervation, responds to pharmacological and gustatory stimuli, and restores salivary flow and oral defence in a defective mouse model, highlighting a path towards organ-level regenerative therapy.

Salivary Gland Function and Hyposalivation Management publication trend

The graph below shows the total number of articles in salivary gland function and hyposalivation management across all publications each year (not limited to Nature Index journals).

Technical terms

Acinar cell: Secretory epithelial cell that produces primary salivary fluid rich in enzymes and mucins.

Myoepithelial cell (MEC): Contractile cell that surrounds acini and assists in saliva expulsion.

Hyposalivation: Objective reduction in salivary flow rate, often leading to xerostomia.

Xerostomia: Subjective sensation of oral dryness irrespective of measured flow.

Fibroblast growth factor receptor (FGFR): Cell-surface receptor mediating FGF signals essential for gland development and differentiation.

Ferroptosis: Iron-dependent, lipid-peroxidation-driven regulated cell death implicated in glandular injury.

Mesenchymal stem cell (MSC): Multipotent stromal cell capable of differentiating and secreting trophic factors for tissue repair.

Sialogogue: Agent that stimulates saliva secretion, either pharmacological or gustatory.

Organ germ: Engineered rudiment that recapitulates early developmental processes to form a functional organ upon transplantation.

References

1. FGFR2 is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation. Nature Communications (2023).
2. Functional salivary gland regeneration by transplantation of a bioengineered organ germ. Nature Communications (2013).
3. Autologous mesenchymal stem cells offer a new paradigm for salivary gland regeneration. International Journal of Oral Science (2023).
4. TGFβ2‐Driven Ferritin Degradation and Subsequent Ferroptosis Underlie Salivary Gland Dysfunction in Postmenopausal Conditions. Advanced Science (2024).
5. Cancer therapy–related salivary dysfunction. Journal of Clinical Investigation (2024).
6. Diagnosis and management of xerostomia and hyposalivation. Therapeutics and Clinical Risk Management (2014).