Increased fluid secretion after adenoviral-mediated transfer of the aquaporin-1 cDNA to irradiated rat salivary glands

Christine Delporte, Brian C. O'Connell, Xinjun He, Henry E. Lancaster, Anne C. O'Connell, Peter Agre, Bruce J. Baum

Research output: Contribution to journalArticle

Abstract

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, hAQPI was localized in the apical and basolateral plasma membranes. Fluid movement across monolayers infected by AdhAQP1 in response to an osmotic gradient was ≃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 14) 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.

Original languageEnglish (US)
Pages (from-to)3268-3273
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number7
DOIs
StatePublished - Apr 1 1997

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Keywords

  • adenovirus
  • gene transfer
  • radiation damage
  • xerostomia

ASJC Scopus subject areas

  • General

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