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Background/Aims: Patients with esophageal atresia (EA) and tracheoesophageal fistula (TEF) often suffer chronic respiratory tract disease. We previously reported that primary lung maldevelopment caused by deficient branching of embryonal airways in experimental EA-TEF was induced by Adriamycin. In this study, we investigated the Vascular endothelial growth factor (VEGF) pathway in the developing lung in an EA-TEF rat model. We further analyzed the effect of recombinant VEGF treatment in vitro on branching morphogenesis of embryo lungs in experimental EA-TEF. Methods: Pregnant rats received either Adriamycin or vehicle on E7, E8 and E9. Lungs were recovered at E15, E18 and E21. Expression of VEGF and receptors (Flk-1 and Flt-1) were assessed by quantitative PCR, immunohistochemistry and immunoblotting. E13 lungs were cultured for 72 hours with 50 ng/mL of recombinant rat VEGF in serum-free medium. The rates of increase in bud count and airway contour were evaluated. Results: Our results showed a significant downregulation of VEGF during pseudoglandular and canalicular stages. In contrast, there were significantly higher levels of the Flt-1 receptor in the canalicular stage, which may represent a compensatory response to decreased VEGF. However, both variables returned to normal levels at the saccular stage. Exogenous VEGF treatment enhanced hypoplastic lung growth, evidenced by the increase in bud count and airway contour. Conclusions: A VEGF signaling defect possibly plays an important role in defective embryonic airway branching. Additionally, VEGF treatment may accelerate lung growth in EA - TEF lungs. [ABSTRACT FROM AUTHOR]

Background: Previous reports showed that prenatal hypoxia delays the process of lung maturation. Vascular endothelial growth factor (VEGF) and its receptors were important for lung development. However, the role of VEGF and VEGF receptors in altered fetal lung development and maturation induced by prenatal hypoxia remains unknown. Objectives: To elucidate the role of VEGF and VEGF receptors in altered fetal lung development and maturation induced by prenatal hypoxia. Methods: Lung sections of control and maternal hypoxic fetal mice were used for the determination of lung development and total RNA isolated from lung homogenates were used for determination of the expression patterns of VEGF, Flt-1, Flk-1, hypoxia-inducible factor (HIF)-1α, HIF-2α, surfactant protein (SP)-A, SP-B, SP-C, and SP-D by quantitative real-time RT-PCR. Results: Prenatal hypoxia resulted in fetal mice body weight gain impairment, delayed fetal pulmonary aeration and maturation. Pulmonary SP-A, SP-B, SP-C, and SP-D mRNA were all decreased in the prenatal hypoxia group. In addition, we demonstrated that prenatal hypoxia inhibited the developmental increase of pulmonary HIF-1α and HIF-2α expression and resulted in decreasing VEGF and its receptors (Flt-1 and Flk-1) at the mRNA expression level and VEGF protein level in fetal lungs. These inhibitory effects persisted and progressed even when the dams were returned to air. Conclusions: We suggest that prenatal hypoxia insults, at least in late gestation, influence pulmonary VEGF and VEGF receptor expression through the down-regulation of HIF pathways and impair fetal lung growth and maturation. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Vascular endothelial growth factor (VEGF) is produced by almost all cancer cells and VEGF receptor 1 (R1) (Flt-1) is abundantly expressed on human monocytes. In the present study, we investigated whether VEGF affects the antibody-dependent cell-mediated cytotoxicity (ADCC) of human monocytes mediated by trastuzumab. Methods: HER-2-expressing tumor cell lines (MKN-7, TE-4 and SKOV-3) were evaluated for trastuzumab-mediated ADCC of human monocytes in the presence of VEGF165. The trastuzumab-mediated, monocyte-derived ADCC were treated with the anti-human blocking VEGF R1 or VEGF R2 mAb. VEGF-induced intracellular signaling on monocytes was quantified with ELISA kits. Results: VEGF partially inhibited the ADCC of human monocytes mediated by trastuzumab. The VEGF-induced deficiency of human monocytes for ADCC was completely recovered by the anti-human blocking VEGF R1 mAb, while the anti-VEGF R2 blocking mAb did not have any effect. Furthermore, VEGF treatment enhanced the phospho-Erk 1/2 in human monocytes. Conclusion: VEGF partially inhibited the ADCC of human monocytes mediated by trastuzumab, and this inhibition was mainly mediated by VEGF R1 (Flt-1). Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aim: We aimed to examine the possible involvement of vascular endothelial growth factor (VEGF) in the pathogenesis of puromycin aminonucleoside nephrosis (PAN). Methods: The expression and localization of the mRNA of VEGF and its receptors, flt-1 and flk-1, were analyzed in the kidneys of puromycin aminonucleoside-injected rats by use of Northern blotting and in situ hybridization. Results: In association with the induction of proteinuria, VEGF mRNA underwent decrease in amount from 3 days after the injection, reaching the minimum level at 7 days, followed by a gradual recovery by 28 days. The levels of flk-1 and flt-1 mRNA showed similar transient decrease in PAN kidney, whereas the mRNA of von Willebrand factor, a marker of endothelial cells, showed no change in amount. In the normal rat kidney, VEGF mRNA was localized primarily to podocytes, and flk-1 mRNA was localized exclusively to endothelial cells with much higher intensity in glomeruli than in peritubular capillaries. In PAN kidney, the intensities of both VEGF and flk-1 signals in podocytes and glomerular endothelial cells, respectively, appeared much lower at 7 days than in normal kidney. Conclusion: These results indicate that the VEGF-VEGF receptor system is downregulated in PAN, implying that it is not involved in the mechanism of proteinuria in PAN.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]