title: DNA demethylating agent decitabine increases AQP5 expression and restores salivary function.
abstract: Xerostomia is the symptom of oral dryness resulting most frequently, but not exclusively, from salivary gland hypofunction. Because the prevalence of xerostomia may increase with age, it has multiple oral health consequences in aging populations. In the present study, we demonstrate that the in vivo administration of 5-aza-2'-deoxycytidine (5-Aza-CdR; decitabine), a DNA demethylating agent, to the murine aging model C57BL/6CrSlc mice (24 wks old) increased the volumes of salivary flow compared with those of control mice. Western blot analysis and immunohistochemical staining demonstrated the augmented expression of AQP5 protein in the salivary glands of 5-Aza-CdR-treated mice compared with those of control mice. In addition, AQP5 protein expression levels in 5-Aza-CdR-treated old mice (27 wks old) were much higher than those in untreated and young mice (6 wks old). Global methylation levels in the salivary glands were significantly lower in the 5-Aza-CdR-treated mice than in the untreated mice. Moreover, the induction of demethylation in the AQP5 promoter of 5-Aza-CdR-treated mice was stronger than in the control mice. Analysis of our data therefore suggests that a DNA demethylating agent may be a useful drug for restoring hyposalivation in elderly individuals, thereby leading to the resolution of xerostomia.
authors.affiliation: Department of Oral Medicine, Institute of Health Biosciences, The University of Tokushima, Graduate Faculty of Dentistry, Tokushima, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yamamura
authors.forename: K
authors.initials: K
authors.lastname: Aota
authors.forename: T
authors.initials: T
authors.lastname: Yamanoi
authors.forename: K
authors.initials: K
authors.lastname: Kani
authors.forename: H
authors.initials: H
authors.lastname: Takano
authors.forename: Y
authors.initials: Y
authors.lastname: Momota
authors.forename: K
authors.initials: K
authors.lastname: Motegi
authors.forename: M
authors.initials: M
authors.lastname: Azuma
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D051402:Aquaporin 5 / Q000096:biosynthesis* / Q000235:genetics; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects*; D015254:DNA Modification Methylases / Q000494:pharmacology*; D000077209:Decitabine; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012463:Saliva / Q000378:metabolism; D012469:Salivary Glands / Q000187:drug effects* / Q000378:metabolism; D012472:Salivation / Q000187:drug effects; D013047:Specific Pathogen-Free Organisms; D014987:Xerostomia / Q000378:metabolism
chemical_list: C496038:Aqp5 protein, mouse; D051402:Aquaporin 5; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine