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Mol Ther. 2014 May;22(5):908-18. doi: 10.1038/mt.2013.286. Epub 2013 Dec 17.

Retrograde ductal administration of the adenovirus-mediated NDRG2 gene leads to improved sialaden hypofunction in estrogen-deficient rats.

Author information

  • 11] Department of Biochemistry and Molecular Biology, The State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi'an, China [2] Department of Oral Biology, Stomatology School, The Fourth Military Medical University, Xi'an, China [3] Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
  • 2Department of Biochemistry and Molecular Biology, The State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi'an, China.
  • 3Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
  • 4Institute of Medical Information, China Academy of Medical Sciences, Beijing, China.
  • 5Department of Oral Biology, Stomatology School, The Fourth Military Medical University, Xi'an, China.

Abstract

One of the most common oral manifestations of menopause is xerostomia. Oral dryness can profoundly affect quality of life and interfere with basic daily functions, such as chewing, deglutition, and speaking. Although the feeling of oral dryness can be ameliorated after estrogen supplementation, the side effects of estrogen greatly restrict its application. We previously found that N-myc downstream-regulated gene 2 (NDRG2) is involved in estrogen-mediated ion and fluid transport in a cell-based model. In the present study, we used an ovariectomized rat model to mimic xerostomia in menopausal women and constructed two adenovirus vectors bearing NDRG2 to validate their therapeutic potential. Ovariectomized rats exhibited severe sialaden hypofunction, including decreased saliva secretion and ion reabsorption as well as increased water intake. Immunohistochemistry revealed that the expression of NDRG2 and Na(+) reabsorption-related Na(+)/K(+)-ATPase and epithelial sodium channels (EnaC) decreased in ovariectomized rat salivary glands. We further showed that the localized delivery of NDRG2 improved the dysfunction of Na(+) and Cl(-) reabsorption. In addition, the saliva flow rate and water drinking recovered to normal. This study elucidates the mechanism of estrogen deficiency-mediated xerostomia or sialaden hypofunction and provides a promising strategy for therapeutic intervention.

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