This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart 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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Baatar, D. Articles by Tarnawski, A. S. Search for Related Content PubMed PubMed Citation Articles by Baatar, D. Articles by Tarnawski, A. S.

(American Journal of Pathology. 2002;161:1449-1457.)
© 2002 American Society for Investigative Pathology

Regular Articles

Esophageal Ulceration Triggers Expression of Hypoxia-Inducible Factor-1 and Activates Vascular Endothelial Growth Factor Gene

Implications for Angiogenesis and Ulcer Healing

Dolgor Baatar^*, Michael K. Jones^*, Koji Tsugawa^*, Rama Pai^*, Woo S. Moon^*, Gou Y. Koh, Injune Kim, Seigo Kitano and Andrzej S. Tarnawski^*

From the Department of Medicine,^* VA Medical Center, Long Beach, California, and the University of California, Irvine, California; the Department of Surgery I, Oita Medical University, Oita, Japan; and Pohang University of Science and Technology, Pohang, South Korea

Our previous studies demonstrated that enhanced epithelial cell proliferation is important for healing of experimental esophageal ulcers. However, the roles of angiogenesis, its major mediator, vascular endothelial growth factor (VEGF), and the mechanism(s) regulating VEGF expression during esophageal ulcer healing remain unknown. Esophageal ulcers were induced in rats by focal application of acetic acid. We studied expressions of hypoxia-inducible transcription factor-1 (HIF-1), an activator of the VEGF gene, and VEGF by reverse transcriptase-polymerase chain reaction, Western blotting, and immunostaining. To determine the efficacy of VEGF gene therapy in esophageal ulcer healing, we studied whether a single local injection of plasmid cDNA encoding recombinant human VEGF₁₆₅ affects ulcer healing and angiogenesis. Esophageal ulceration induced HIF-1 protein expression and VEGF gene activation reflected by increased VEGF mRNA (240%) and VEGF protein (310%) levels. HIF-1 protein was expressed in microvessels bordering necrosis where it co-localized with VEGF. Injection of cDNA encoding VEGF₁₆₅ significantly enhanced angiogenesis and accelerated esophageal ulcer healing. These results: 1) suggest that HIF-1 may mediate esophageal ulceration-triggered VEGF gene activation, 2) indicate an essential role of VEGF and angiogenesis in esophageal ulcer healing, and 3) demonstrate the feasibility of gene therapy for the treatment of esophageal ulcers.

This article has been cited by other articles:

				H. Jeon, H. Kim, D. Choi, D. Kim, S.-Y. Park, Y.-J. Kim, Y. M. Kim, and Y. Jung Quercetin Activates an Angiogenic Pathway, Hypoxia Inducible Factor (HIF)-1-Vascular Endothelial Growth Factor, by Inhibiting HIF-Prolyl Hydroxylase: a Structural Analysis of Quercetin for Inhibiting HIF-Prolyl Hydroxylase Mol. Pharmacol., June 1, 2007; 71(6): 1676 - 1684. [Abstract] [Full Text] [PDF]

				J. Chai, M. Norng, A. S Tarnawski, and J. Chow A critical role of serum response factor in myofibroblast differentiation during experimental oesophageal ulcer healing in rats Gut, May 1, 2007; 56(5): 621 - 630. [Abstract] [Full Text] [PDF]

				M Yeo, D-K Kim, S U Han, J E Lee, Y B Kim, Y K Cho, J H Kim, S W Cho, and K-B Hahm Novel action of gastric proton pump inhibitor on suppression of Helicobacter pylori induced angiogenesis Gut, January 1, 2006; 55(1): 26 - 33. [Abstract] [Full Text] [PDF]

				M. D. Basson Gut Mucosal Healing : Is the Science Relevant? Am. J. Pathol., October 1, 2002; 161(4): 1101 - 1105. [Full Text] [PDF]