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.
نویسندگان
چکیده
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 beta-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 beta-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.
منابع مشابه
Comparison of Effects of High-Fat, High-Protein and Low-Calorie Diets on Klotho Gene Expression and TGF-β Level in Serum and Liver of Old Male Wistar Rats
Background and Objectives: Different diets have important roles in human health and aging. In the current study, we aimed to characterize the Klotho, an anti-aging protein, gene expression and protein level in the serum and assess the protein levels of Transforming growth factor-β and Platelet-derived growth factor in old rats which treated with different diets (high-fat, high-protein, low calo...
متن کاملMolecular Study of Vascular Endothelial Growth Factor Gene in Iranian Patients after Myocardial Infarction
Background: Stimulation of collateral artery growth (arteriogenesis) and/or capillary network growth (angiogenesis) would be beneficial to the patients with myocardial infarction. To understand the central role of vascular endothelial growth factor (VEGF) in biological angiogenesis, we performed molecular analysis of the VEGF gene in patients afflicted with acute myocardial infarction (AMI). Me...
متن کاملVascular Endothelial Growth Factor from Embryonic Status to Cardiovascular Pathology
Vascular endothelial growth factor (VEGF) is a multifunctional cytokine with distinct functions in angiogenesis, lymphangiogenesis, vascular permeability, and hematopoiesis. VEGF is a highly conserved, disulfide-bonded dimeric glycoprotein of 34 to 45 kDa produced by several cell types including fibroblasts, neutrophils, endothelial cells, and peripheral blood mononuclear cells, particularly T ...
متن کاملThe Effect of Aerobic Training on Tumor Necrosis Factor alpha, Hypoxia-Inducible Factor-1 alpha & Vascular Endothelial Growth Factor Gene Expression in Cardiac Tissue of Diabetic Rats
Objective: The goal of this research was to determine the influence of 4 weeks aerobic training on gene expression of tumor necrosis factor alpha (TNF-α), hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) in the cardiac tissue of diabetic rats. Materials and Methods: In an experimental study, 30 male wistar rats were partitioned into three groups (n=10), d...
متن کاملSynergistic Effects of Graphene Oxide and Vascular Endothelial Growth Factor Immobilized in Polycaprolactone Nanofiber as a Candidate for Diabetic Wound Healing
Background & Objective: The combination of two or more therapeutic agents and their synergetic impacts can be therapeutically effective against multifactorial diseases, such as diabetic foot ulcers. This study demonstrates the application of a nanofiber-based drug delivery system with a controlled release of the growth factor. Various studies have shown that vascular endothelial growth facto...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Journal of pharmacology and experimental therapeutics
دوره 311 3 شماره
صفحات -
تاریخ انتشار 2004