Yan Li, Shaoqing Li, Wugang Hou, Hailong Dong, Libo Yao and Lize Xiong
Scientific Tracks Abstracts: J Stem Cell Res Ther
Xerostomia is a subjective symptom and prevalent in more than one-third of postmenopausal women who usually complaint of seriously interfered chewing, deglutition, and speaking. Saliva production is subjected to the processes of a plasma-like, isotonic primary secretion in salivary acini and subsequent re-absorption of Na+ and Cl− in the collecting ducts, leaving hypotonic saliva into the oral cavity. Some xerostomia patients actually do not suffer from decreased saliva secretion but from the increased ionic osmotic pressure or viscidity of saliva. Although the feeling of oral dryness can be ameliorated with estrogen supplementation administration, the side effects of estrogen greatly restrict its application. We found that N-myc downstream regulated gene 2 (NDRG2) is involved in estrogen-mediated Na+ and Cl− transport in salivary ductal cells. In addition, an ovariectomized rat model was used to mimic xerostomia in postmenopausal women and adenovirus vectors bearing NDRG2 were constructed to validate their therapeutic potential. Ovariectomized rats exhibited severe sialaden hypofunction, including decreased saliva secretion and ion re-absorption, as well as increased water consumption. It was also found that the expression of NDRG2, Na+/K+-ATPase, and epithelial sodium channels (EnaC) decreased in ovariectomized rat salivary glands, which are all involved in Na+ re-absorption. Retrograde ductal delivery of NDRG2 adenovirus in ovariectomized rat through submandibular gland can efficiently improve the dysfunction of Na+ and Cl− re-absorption, and promote saliva flow rate and water intake return to normal levels. This study elucidates the underling mechanism of estrogen deficiency-mediated xerostomia and provides an attractive strategy for therapeutic intervention.
Yan Li has completed her PhD from the Fourth Military Medical University (China) in 2009 and she used to be a Visiting Scholar for Post-doctoral research in Purdue University (USA). Now she is a Lecturer of the Department of Biochemistry and Molecular Biology, the Fourth Military Medical University (China). She has published more than 30 papers in reputed journals, including J BiolChem, MolTher, Breast Cancer Res, and Cell Death Dis.