The Fourth Military Medical University, China
Yan Li has completed her Ph.D. 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.
Xerostomia is a subjective symptom and prevalent in more than one-third of postmenopausal women usually complainof seriouslyinterferedchewing, deglutition, and speaking. Saliva production is subjected to the processes of a plasma-like, isotonic primary secretion insalivary acini and subsequent reabsorption ofNa+ and Cl- in the collecting ducts, leavinghypotonic saliva into the oralcavity.Some xerostomia patients actually do not suffer from decreasedsaliva secretionbut from the increasedionic osmotic pressure orviscidity 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 downstreamregulated 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 NDRG2were constructed to validate their therapeutic potential. Ovariectomized rats exhibited severe sialadenhypofunction, including decreased saliva secretion and ion reabsorption, as well as increased water consumption.We 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 inNa+reabsorption. Retrograde ductal delivery ofNDRG2adenovirusin ovariectomized ratthroughsubmandibular glandcan efficient lyimprove the dysfunction of Na+ and Cl− reabsorption, and promote saliva flow rate and water intakereturn to normal levels. This study elucidates theunderling mechanismof estrogen deficiency-mediated xerostomia and provides an attractive strategy for therapeutic intervention.