QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.104.071464v1 311/3/982    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Deng, X. Articles by Yoshida, M. Search for Related Content PubMed PubMed Citation Articles by Deng, X. Articles by Yoshida, M.

GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Gene Therapy with Adenoviral Plasmids or Naked DNA of Vascular Endothelial Growth Factor and Platelet-Derived Growth Factor Accelerates Healing of Duodenal Ulcer in Rats

Pathology and Laboratory Medicine Service, Diagnostic and Molecular Medicine Health Care Group, Veterans Affairs Medical Center (X.D., S.S., T.K., M.R.J., M.Y.) and Departments of Pathology (X.D., S.S., T.K., M.R.J.) and Pharmacology (S.S.), University of California-Irvine, Long Beach, California

After we demonstrated that daily intragastric administration of angiogenic growth factors like basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), or vascular endothelial growth factor (VEGF) accelerated the healing of chronic duodenal ulcers in rats, we hypothesized that a single dose of gene therapy related to these growth factors may be enough to accelerate the healing of duodenal ulcers through enhancement of synthesis of endogenous angiogenic growth factors. Thus, we compared the effects of intraduodenal or intravenous adenoviral vectors and naked DNA transducing the genes for either VEGF or PDGF in experimental duodenal ulcers induced by cysteamine in rats. Sprague-Dawley female rats with confirmed duodenal ulcers were randomly divided into control and treatment groups. The controls received either intraduodenal injection of buffer or the -galactosidase-transducing adenoviral vector. Rats treated with a single or double dose of adenoviral vector or naked DNA of VEGF or PDGF had significantly smaller ulcers than the controls. Histologic analysis demonstrated that reepithelized granulation tissue with prominent angiogenesis replaced the ulcers. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assay of duodenal mucosa confirmed that the expression of VEGF or PDGF proteins was enhanced by the transgenes, whereas -galactosidase staining in multiple organs identified that the transgenes, especially after local administration were only localized in the duodenum, stomach, and jejunum. These results suggest that gene therapy with either VEGF or PDGF may be a rapid approach to achieve duodenal ulcer healing.

Address correspondence to: Dr. Sandor Szabo, Veterans Affairs Medical Center, 5901 E. 7th Street, Long Beach, CA 90822. E-mail: sandor.szabo{at}med.va.gov