Pharmacological activation of the EDA/EDAR signaling pathway restores salivary gland function following radiation-induced damage.

Abstract

Radiotherapy of head and neck cancers often results in collateral damage to adjacent salivary glands associated with clinically significant hyposalivation and xerostomia. Due to the reduced capacity of salivary glands to regenerate, hyposalivation is treated by substitution with artificial saliva, rather than through functional restoration of the glands. During embryogenesis, the ectodysplasin/ectodysplasin receptor (EDA/EDAR) signaling pathway is a critical element in the development and growth of salivary glands. We have assessed the effects of pharmacological activation of this pathway in a mouse model of radiation-induced salivary gland dysfunction. We report that post-irradiation administration of an EDAR-agonist monoclonal antibody (mAbEDAR1) normalizes function of radiation damaged adult salivary glands as determined by stimulated salivary flow rates. In addition, salivary gland structure and homeostasis is restored to pre-irradiation levels. These results suggest that transient activation of pathways involved in salivary gland development could facilitate regeneration and restoration of function following damage.

• Authors: Grace Hill, Denis Headon, Zoey I Harris, Kenneth Huttner, Kirsten H Limesand
• Journal: PloS one (PLoS One) Vol. 9 Issue 11 Pg. e112840 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25409170 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Ectodysplasins
• Eda protein, mouse
• Edar Receptor
• Edar protein, mouse
• Amylases

Topics

• Amylases (metabolism)
• Animals
• Antibodies, Monoclonal (immunology, pharmacology)
• Cell Proliferation (drug effects, radiation effects)
• Ectodysplasins (metabolism)
• Edar Receptor (immunology, metabolism)
• Female
• Head and Neck Neoplasms (radiotherapy)
• Mice
• Recovery of Function (drug effects, radiation effects)
• Saliva (drug effects, metabolism, radiation effects)
• Salivary Glands (cytology, drug effects, physiology, radiation effects)
• Signal Transduction (drug effects, radiation effects)
• Time Factors
• Vacuoles (drug effects, radiation effects)