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DNA demethylating agent decitabine increases AQP5 expression and restores salivary function
Y Yamamura1, K Aota, T Yamanoi
1Department of Oral Medicine, Institute of Health Biosciences, The University of Tokushima, Graduate Faculty of Dentistry, Tokushima, Japan.
Journal of Dental Research
|April 24, 2012
Summary
DNA demethylating agents, like decitabine (5-Aza-CdR), can restore salivary flow in aging mice. This research suggests potential treatments for age-related dry mouth (xerostomia) by targeting salivary gland function.
Area of Science:
- Gerontology
- Molecular Biology
- Oral Medicine
Background:
- Xerostomia (dry mouth) is a common symptom in aging populations, often linked to reduced salivary gland function.
- Age-related xerostomia can lead to significant oral health issues in elderly individuals.
Purpose of the Study:
- To investigate the potential of DNA demethylating agents to restore salivary flow in an aging mouse model.
- To explore the molecular mechanisms underlying the effects of decitabine on salivary gland function and AQP5 expression.
Main Methods:
- Administration of 5-aza-2'-deoxycytidine (decitabine), a DNA demethylating agent, to aging C57BL/6CrSlc mice.
- Assessment of salivary flow volume, AQP5 protein expression via Western blot and immunohistochemistry, and global DNA methylation levels.
- Analysis of AQP5 promoter methylation status.
Main Results:
- Decitabine treatment significantly increased salivary flow volumes in aging mice compared to controls.
- Augmented expression of Aquaporin-5 (AQP5) protein was observed in the salivary glands of decitabine-treated mice.
- Decitabine reduced global DNA methylation and induced demethylation in the AQP5 promoter in salivary glands.
Conclusions:
- DNA demethylating agents, such as decitabine, show promise for treating hyposalivation and xerostomia in the elderly.
- The mechanism involves increased AQP5 expression, potentially mediated by epigenetic modifications in the salivary glands.
