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Updated: May 1, 2026
Retroductal Submandibular Gland Instillation and Localized Fractionated Irradiation in a Rat Model of Salivary Hypofunction
Published on: April 24, 2016
Rapamycin delays salivary gland atrophy following ductal ligation
S S Bozorgi1, G B Proctor1, G H Carpenter1
1King's College London Dental Institute, Salivary Research Unit, Floor 17, Tower Wing, London, UK.
Abstract:
Salivary gland atrophy is a frequent consequence of head and neck cancer irradiation therapy but can potentially be regulated through the mammalian target of rapamycin (mTOR). Excretory duct ligation of the mouse submandibular gland provokes severe glandular atrophy causing activation of mTOR. This study aims to discover the effects of blocking mTOR signaling in ligation-induced atrophic salivary glands. Following 1 week of unilateral submandibular excretory duct ligation: gland weights were significantly reduced, 4E-BP1 and S6rp were activated, and tissue morphology revealed typical signs of atrophy. However, 3 days following ligation with rapamycin treatment, a selective mTOR inhibitor, gland weights were maintained, 4E-BP1 and S6rp phosphorylation was inhibited, and there were morphological signs of recovery from atrophy. However, following 5 and 7 days of ligation and rapamycin treatment, glands expressed active mTOR and showed signs of considerable atrophy. This evidence suggests that inhibition of mTOR by rapamycin delays ligation-induced atrophy of salivary glands.
Insights
Rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), temporarily delays salivary gland atrophy caused by duct ligation in mice. However, prolonged treatment shows continued gland atrophy, suggesting mTOR inhibition only offers short-term benefits.
Area of Science:
- Cell Biology
- Oncology
- Regenerative Medicine
Background:
- Head and neck cancer radiation therapy frequently causes salivary gland atrophy.
- The mammalian target of rapamycin (mTOR) pathway is implicated in regulating salivary gland function and atrophy.
- Submandibular gland excretory duct ligation in mice induces atrophy and activates mTOR signaling.
Purpose of the Study:
- To investigate the effects of inhibiting mTOR signaling on salivary gland atrophy induced by duct ligation.
- To determine the therapeutic potential of rapamycin in preventing or reversing salivary gland atrophy.
Main Methods:
- Unilateral submandibular excretory duct ligation in mice.
- Treatment with rapamycin, a selective mTOR inhibitor.
- Assessment of gland weight, protein activation (4E-BP1, S6rp), and tissue morphology at various time points.
Main Results:
- Duct ligation led to significant gland weight reduction, 4E-BP1 and S6rp activation, and atrophic changes.
- Short-term rapamycin treatment (3 days) maintained gland weight, inhibited mTOR pathway activation, and showed signs of recovery.
- Long-term rapamycin treatment (5 and 7 days) resulted in active mTOR signaling and considerable atrophy.
Conclusions:
- Inhibition of mTOR by rapamycin can delay the onset of ligation-induced salivary gland atrophy.
- The protective effect of rapamycin appears to be transient, with atrophy resuming upon prolonged treatment.
- Further research is needed to explore sustained therapeutic strategies targeting salivary gland regeneration.
