Increased fluid secretion after adenoviral-mediated transfer of the aquaporin-1 cDNA to irradiated rat salivary glands.
A replication-deficient, recombinant adenovirus encoding human aquaporin-1 (hAQP1), the archetypal water channel, was constructed. This virus, AdhAQP1, directed hAQP1 expression in several epithelial cell lines in vitro. In polarized MDCK cell monolayers, hAQP1 was localized in the apical and basolateral plasma membranes. Fluid movement across monolayers infected by AdhAQP1 in response to an osmotic gradient was approximately 4-fold that seen with uninfected monolayers or monolayers infected by a control virus. When AdhAQP1 was administered to rat submandibular glands by retrograde ductal instillation, significant hAQP1 expression was observed by Western blot analysis in crude plasma membranes and by immunohistochemical staining in both acinar and ductal cells. Three or four months after exposure to a single radiation dose (17.5 or 21 Gy, respectively), AdhAQP1 administration to rat submandibular glands led to a two- to threefold increase in salivary secretion compared with secretion from glands administered a control virus. These results suggest that hAQP1 gene transfer may have potential as an unique approach for the treatment of postradiation salivary hypofunction.
Delporte
C
C
Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892-1190, USA.
O'Connell
B C
BC
He
X
X
Lancaster
H E
HE
O'Connell
A C
AC
Agre
P
P
Baum
B J
BJ
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D051398:Aquaporin 1; D020346:Aquaporins; D001789:Blood Group Antigens; D002460:Cell Line; D018076:DNA, Complementary; D004285:Dogs; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000235:genetics; D012463:Saliva / Q000378:metabolism*; D013363:Submandibular Gland / Q000378:metabolism* / Q000528:radiation effects
C496020:AQP1 protein, human; C496022:Aqp1 protein, rat; D020346:Aquaporins; D001789:Blood Group Antigens; D018076:DNA, Complementary; D007473:Ion Channels; D011994:Recombinant Proteins; D051398:Aquaporin 1