• Journal of Microbiology and Biotechnology
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• v.18 no.1
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• pp.183-187
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• 2008

Vascular endothelial growth factors (VEGFs) are a family of proteins that mediate angiogenesis. $VEGF_{165}$ is a VEGF-A isoform and has been extensively studied owing to its potential use in therapeutic angiogenesis. This study established Chinese hamster ovary (CHO) cells overexpressing recombinant human $VEGF_{165}$ $(rhVEGF_{165})$ protein. The production rate of the established CHO cells was over 80mg/l of $rhVEGF_{165}$ protein from a 7-day batch culture process using a 7.5-l bioreactor with a 5-l working volume and serum-free medium. The $rhVEGF_{165}$ protein was purified to homogeneity from the culture supernatant using a two-step chromatographic procedure that resulted in a 48% recovery rate. The purified $rhVEGF_{165}$ protein was a glycosylated homodimeric protein with a higher molecular weight (MW) than the protein expressed from insect cells, suggesting that the glycosylation of the $rhVEGF_{165}$ protein in CHO cells differed from that in insect cells. The purified $rhVEGF_{165}$ protein in this study was functionally active with a half-maximal effective concentration of 3.8ng/ml and specific activity of $2.5{\times}10^5U/mg$.

• Korean Journal of Head & Neck Oncology
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• v.21 no.2
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• pp.183-189
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• 2005

Objectives: Angiogenesis is the process of new blood vessel development from preexisting vessel. The growth of tumor is dependent on angiogenesis. This study was aimed to determine the role of the VEGF expression and MVD(microvessel density) in salivary gland tumors and to analyze the correlation between the expression of VEGF/MVD, and clinical manifestation. Material and Methods: We analyzed the expression of VEGF and average MVD and neo-MVD in the 57 cases of salivary gland tumors by immunohistochemistry. Results: VEGF expression was higher in malignant tumors than in benign tumors. Average and neo-MVD were not different in benign tumor and malignant tumor. There was a tendency of positive correlation between VEGF expression and MVD but it was not statistically significant. Stage, T stage and recurrance rate were not correlated with VEGF expression, average-MVD and neo-MVD. Expression of VEGF, average-MVD and neo-MVD were significantly increased in Warthin's tumor compared with pleomorphic adenoma. Conclusion: Overexpression of VEGF has an important role in malignant salivary gland tumors.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.4
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• pp.281-289
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• 2019

Vascular endothelial growth factor (VEGF)-C and its receptor, vascular endothelial growth factor receptor (VEGFR)-3, are responsible for lymphangiogenesis in both embryos and adults. In epilepsy, the expression of VEGF-C and VEGFR-3 was significantly upregulated in the human brains affected with temporal lobe epilepsy. Moreover, pharmacologic inhibition of VEGF receptors after acute seizures could suppress the generation of spontaneous recurrent seizures, suggesting a critical role of VEGF-related signaling in epilepsy. Therefore, in the present study, the spatiotemporal expression of VEGF-C and VEGFR-3 against pilocarpine-induced status epilepticus (SE) was investigated in C57BL/6N mice using immunohistochemistry. At 1 day after SE, hippocampal astrocytes and microglia were activated. Pyramidal neuronal death was observed at 4 days after SE. In the subpyramidal zone, VEGF-C expression gradually increased and peaked at 7 days after SE, while VEGFR-3 was significantly upregulated at 4 days after SE and began to decrease at 7 days after SE. Most VEGF-C/VEGFR-3-expressing cells were pyramidal neurons, but VEGF-C was also observed in some astrocytes in sham-manipulated animals. However, at 4 days and 7 days after SE, both VEGFR-3 and VEGF-C immunoreactivities were observed mainly in astrocytes and in some microglia of the stratum radiatum and lacunosum-moleculare of the hippocampus, respectively. These data indicate that VEGF-C and VEGFR-3 can be upregulated in hippocampal astrocytes and microglia after pilocarpine-induced SE, providing basic information about VEGF-C and VEGFR-3 expression patterns following acute seizures.

• Molecules and Cells
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• v.28 no.1
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• pp.1-5
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• 2009

Vascular endothelial growth factor (VEGF) is essential for many angiogenic processes both in normal and pathological conditions. However, the signaling pathways involved in VEGF-induced angiogenesis are incompletely understood. The protein kinase D1 (PKD1), a newly described calcium/calmodulin-dependent serine/threonine kinase, has been implicated in cell migration, proliferation and membrane trafficking. Increasing evidence suggests critical roles for PKD1-mediated signaling pathways in endothelial cells, particularly in the regulation of VEGF-induced angiogenesis. Recent studies show that class IIa histone deacetylases (HDACs) are PKD1 substrates and VEGF signal-responsive repressors of myocyte enhancer factor-2 (MEF2) transcriptional activation in endothelial cells. This review provides a guide to PKD1 signaling pathways and the direct downstream targets of PKD1 in VEGF signaling, and suggests important functions of PKD1 in angiogenesis.

• Clinical and Experimental Pediatrics
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• v.50 no.12
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• pp.1241-1246
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• 2007

Purpose : Recently, there has been several studies to clarify the pathogenesis of Kawasaki disease (KD) and the relations of VEGF and endostatin that act on vascular endothelial cells to the coronary artery complications. In this report, we measured serum levels of VEGF and endostatin in acute and subacute phases of KD to assess the change of these levels and the relations to the development of coronary artery lesions (CAL). Methods : Twenty six patients were diagnosed and treated for KD between January, 2001 and July, 2005 at Kangnam St. Mary's Hospital, the Catholic University of Korea. They were divided into those with and without CAL. Serum levels of VEGF and endostatin were measured during acute and subacute phases and compared to those measured in healthy and disease control groups. Results : Serum levels of VEGF were increased in KD but no differences were noted in KD with and without CAL. Serum levels of endostatin were decreased in the acute phase of KD, however they were recovered in the subacute phase of KD, regardless of CAL. The VEGF/endostatin ratio was increased in KD. KD without CAL showed a relative decrease in this ratio during the subacute phase. Significant positive correlations were found between serum VEGF and WBC count, VEGF and ESR, VEGF/endostatin ratio and ESR in the acute phase of KD. Conclusion : Analysis of factors influencing the vascular endothelium such as VEGF and endostatin will help to clarify the etiology of KD and the pathogenesis of CAL.

• Tuberculosis and Respiratory Diseases
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• v.51 no.6
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• pp.530-539
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• 2001

Background : Bronchial asthma is an inflammatory disease of the airways that is associated with airway remodeling. The vascular endothelial growth factor (VEGF) is a potent, multifunctional cytokine that contributes to angiogenesis and inflammation. Matrix metalloproteinase-9 (MMP-9) is a major proteolytic enzyme that in duces bronchial remodeling in asthma. However, there is no data available on the possible role of the VEGF or on the potential relationship between the VEGF and MMP-9 in acute asthma. Therefore, the VEGF was studied to determine whether or not it participates in airway inflammation during acute asthma. An additional aim of this study was to determine whether or not the VEGF levels correlated with the MMP-9 levels in the sputum of acute asthma patients. Methods: Both the VEGF and MMP-9 levels were measured by an enzyme immunoassay and zymographic analysis in the sputum of patients with either stable asthma or with acute asthma. The VEGF and MMP-9 levels were also evaluated during a spontaneous asthma attack. Results : The VEGF levels were significantly higher in the sputum of acute asthmatic patients than in either the stable patients the control subjects. The VEGF levels in the sputum during asthma exacerbation were significantly higher than those on the remission days, and those levels decreased after asthma therapy. In acute asthmatic patients, the VEGF levels in the sputum correlated with the number of neutrophils and eosinophils. In addition, a significant correlation was established between the VEGF and MMP-9 levels in the sputum. Conclusion : These results suggest that VEGF overproduction is associated with airway inflammation during acute asthma and is related to the MMP-9 function.

• Clinical and Experimental Pediatrics
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• v.51 no.8
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• pp.879-885
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• 2008

Purpose : The human lung fibroblast may act as an immunomodulatory cell by providing pro-inflammatory cytokines and chemokines, which are important in airway remodeling. Vascular endothelial growth factor (VEGF) induces mucosal edema and angiogenesis. Thymus and activation regulated chemokine (TARC) induces selective migration of T helper 2 cells. We investigated whether human lung fibroblasts produced VEGF and TARC, and the effects were augmented with the co-culture of fibroblasts and human bronchial smooth muscle cells (HBSMC), and whether dexamethasone can inhibit the proliferation and the release of VEGF in lung fibroblasts. Methods : Human lung fibroblasts were cultured with and without HBSMC, growth-arrested in serum-deprived medium, and pretreated with dexamethasone for 16 hours. After 24-hour stimulation with platelet derived growth factor-BB (PDGF-BB) and/or transforming growth factor-${\beta}$ (TGF-${\beta}$), culture supernatant was harvested for assays of VEGF and TARC. Cell proliferation was assayed using BrdU cell proliferation ELISA kit. Results : 1) The release of VEGF was significantly increased after stimulation with TGF-${\beta}$, and its release was augmented when co-stimulated with PDGF and TGF-${\beta}$. 2) VEGF release induced by PDGF or TGF-${\beta}$ was inhibited by dexamethasone. 3) There was no synergistic effect on the release of VEGF when human lung fibroblasts were co-cultured with HBSMC. 4) Dexamethasone did not suppress human lung fibroblasts proliferations. 5) Neither TGF-${\beta}$ nor PDGF induced TARC release from lung fibroblasts. Conclusion : Human lung fibroblasts may modulate airway remodeling by release of VEGF, but they have no synergistic effects when co-cultured with HBSMC. Dexamethasone suppresses VEGF release, not proliferation of lung fibroblast.

• Applied Microscopy
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• v.39 no.2
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• pp.81-87
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• 2009

Diabetic retinopathy is one of major complications of diabetes mellitus, which is associated with the dysfunction of retina. It has been reported that the onset of diabetic retinopathy is related to the activation of renin-angiotensin system (RAS). Angiotensin converting enzyme (ACE), which converts angiotensin I into angiotensin II, is a key component of RAS. Among many growth factors, vascualr endothelial growth factor (VEGF) is an important cytokine in the neovasculization of retina, which is a characteristics of diabetic retinopathy. However, the relationship between ACE and VEGF was not elucidated in diabetic retinopathy. Thus, this study was conducted to examine the protective effect of captopril, an ACE inhibitor, in the retina of streptozotocin (STZ)-treated diabetic rats. In present study, STZ-treated diabetic rats exhibited the increase of VEGF levels in serum and retina. The serum levels of VEGF in STZ-treated diabetic rats was not blocked by the treatment of captopril. However, the retina levels of VEGF in STZ-treated diabetic rats was blocked by the treatment of captopril, suggesting the local action of captopril in retina. Immunohistochemical analysis also revealed that the retina of STZ-treated diabetic rats manifested the increase of ganglion cell layers, outer nuclear layers, and inner nuclear layers, which were also prevented by the treatment of captopril. In conclusion, captopril prevented the expression of VEGF in the retina of STZ-treated diabetic rats.

• Tuberculosis and Respiratory Diseases
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• v.62 no.1
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• pp.43-50
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• 2007

Background: Mutated or deregulated expression of C-erbB-2 causes this gene to function as a potent oncogene. Vascular endothelial growth factor (VEGF) is a crucial angiogenic molecule in lung cancer. Both C-erbB-2 and VEGF can promote growth, proliferation and metastasis in non-small cell lung cancer (NSCLC). The purpose of this study was to investigate evaluate the relationship between the expressions of the C-erbB-2 and VEGF genes using immunohistochemistry. Materials and Methods: Ninety-five patients with NSCLC were involved (60 squamous cell carcinoma and 35 adenocarcinoma). The formalin-fixed paraffin embedded specimens were immunohistochemically stained for C-erbB-2 and VEGF using the avidin-biotin complex method. Results: Positive C-erbB-2 expression was observed more often in adenocarcinomas than squamous cell carcinomas (p<0.05). Although the immunohistochemical expressions of C-erbB-2 and VEGF in non-small-cell lung cancer showed increased tendencies at an advanced stage, the correlation between early and advanced cancers was insignificant. In adenocarcinomas, the expressions of VEGF and C-erbB-2 were significantly (p<0.05). Conclusion: The overexpression fo C-erbB-2 was significantly higher in adenocarcinomas than squamous cell carcinomas, and correlated with the expression of VEGF in adenocarcinomas of the lungs.

• BMB Reports
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• v.49 no.3
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• pp.191-196
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• 2016

Vascular endothelial growth factor (VEGF) is a key mediator of angiogenesis and critical for normal embryonic development and repair of pathophysiological conditions in adults. Although phospholipase D (PLD) activity has been implicated in angiogenic processes, its role in VEGF signaling during angiogenesis in mammals is unclear. Here, we found that silencing of PLD2 by siRNA blocked VEGF-mediated signaling in immortalized human umbilical vein endothelial cells (iHUVECs). Also, VEGF-induced endothelial cell survival, proliferation, migration, and tube formation were inhibited by PLD2 silencing. Furthermore, while Pld2-knockout mice exhibited normal development, loss of PLD2 inhibited VEGF-mediated ex vivo angiogenesis. These findings suggest that PLD2 functions as a key mediator in the VEGF-mediated angiogenic functions of endothelial cells.