title: Rapamycin delays salivary gland atrophy following ductal ligation.
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.
authors.affiliation: King's College London Dental Institute, Salivary Research Unit, Floor 17, Tower Wing, London, UK.
authors.forename: S S
authors.initials: SS
authors.lastname: Bozorgi
authors.affiliation: King's College London Dental Institute, Salivary Research Unit, Floor 17, Tower Wing, London, UK.
authors.forename: G B
authors.initials: GB
authors.lastname: Proctor
authors.affiliation: King's College London Dental Institute, Salivary Research Unit, Floor 17, Tower Wing, London, UK.
authors.forename: G H
authors.initials: GH
authors.lastname: Carpenter
mesh_terms: D061354:Acinar Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001284:Atrophy; D005260:Female; D015151:Immunoblotting; D008026:Ligation; D008813:Mice, Inbred ICR; D009929:Organ Size / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D038601:Ribosomal Protein S6 / Q000378:metabolism; D018987:Salivary Ducts / Q000187:drug effects / Q000473:pathology* / Q000601:surgery*; D020123:Sirolimus / Q000494:pharmacology*; D013194:Staining and Labeling; D013363:Submandibular Gland / Q000187:drug effects / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors
chemical_list: D038601:Ribosomal Protein S6; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus