Adenovirus-mediated hAQP1 expression in irradiated mouse salivary glands causes recovery of saliva secretion by...

Area of Science:

• Biomedical Engineering
• Molecular Biology
• Oncology

Background:

• Head and neck irradiation (IR) causes significant salivary gland dysfunction, leading to irreversible saliva secretion loss.
• The precise mechanisms behind radiation-induced salivary hypofunction and effective therapeutic strategies remain elusive.
• Adenoviral vector delivery of human aquaporin-1 (hAQP1) has shown promise in restoring salivary function in preclinical and clinical studies.

Purpose of the Study:

• To investigate the mechanism of salivary secretion loss post-IR.
• To elucidate the functional basis of AdhAQP1-mediated recovery in radiation-compromised salivary glands.
• To assess the impact of hAQP1 expression on salivary gland water transport and secretion.

Main Methods:

• Submandibular gland function was assessed in control mice and mice 2 and 8 months post-IR.
• Salivary secretion and carbachol (CCh)-stimulated acinar cell volume changes were monitored in vitro.
• Adenoviral vector encoding hAQP1 was delivered to salivary glands to evaluate its therapeutic effect.

Main Results:

• Mice post-IR exhibited a sustained 60% loss in fluid secretion and attenuated CCh-induced acinar cell volume reduction.
• hAQP1 expression in non-irradiated mice showed minimal effects, except for an increased initial shrinkage rate in the 8-month group.
• hAQP1 delivery to irradiated glands restored salivary fluid secretion and acinar cell volume dynamics to levels comparable to controls.

Conclusions:

• The data suggest that radiation impairs salivary gland fluid secretion by reducing acinar cell water permeability.
• Expression of hAQP1 enhances water permeability in salivary acinar cells, thereby restoring fluid secretion.
• hAQP1 gene therapy represents a viable strategy for treating radiation-induced salivary hypofunction and alleviating dry mouth symptoms.