title: Retrograde ductal administration of the adenovirus-mediated NDRG2 gene leads to improved sialaden hypofunction in estrogen-deficient rats.
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.
authors.affiliation: 1] 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.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, The State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi'an, China.
authors.forename: Changhao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Wugang
authors.initials: W
authors.lastname: Hou
authors.affiliation: Institute of Medical Information, China Academy of Medical Sciences, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, The State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi'an, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Biochemistry and Molecular Biology, The State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi'an, China.
authors.forename: Kaifeng
authors.initials: K
authors.lastname: Lin
authors.affiliation: Department of Oral Biology, Stomatology School, The Fourth Military Medical University, Xi'an, China.
authors.forename: Zhenqiang
authors.initials: Z
authors.lastname: Situ
authors.affiliation: Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Department of Oral Biology, Stomatology School, The Fourth Military Medical University, Xi'an, China.
authors.forename: Shaoqing
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, The State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi'an, China.
authors.forename: Libo
authors.initials: L
authors.lastname: Yao
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D004967:Estrogens / Q000172:deficiency / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006801:Humans; D008593:Menopause / Q000235:genetics; D010052:Ovariectomy; D051381:Rats; D012469:Salivary Glands; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D014987:Xerostomia / Q000235:genetics* / Q000473:pathology / Q000628:therapy
chemical_list: D004967:Estrogens; C466228:NDRG2 protein, human; D025521:Tumor Suppressor Proteins; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase