Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular endothelial growth factor is a powerful mitogen for endothelial cells, recently reported to be produced by keratinocytes. In the present work, we examined human keratinocytes in primary culture for the splice variants of vascular endothelial growth factor. In situ hybridization revealed that 100% of cultured human keratinocytes expressed mRNA for this cytokine, and analysis by reverse transcriptase-polymerase chain reaction indicated that three species of mRNA were produced. Southern hybridization and size calculations of PCR products revealed mRNA species corresponding to 121, 165, and 189 amino-acid forms of this cytokine. Using a rabbit anti-vascular endothelial growth factor antiserum, we radioimmunoprecipitated two molecular weight forms (approximately 45 and 58 kDa, non-reducing conditions) from keratinocyte culture supernatants. Under reducing conditions, three bands of approximately 15, 20, and 24 kDa appeared, corresponding with the predominant forms of vascular endothelial growth factor described. We propose that secretion of vascular endothelial growth factor by human keratinocytes in vivo sustains angiogenesis during physiologic tissue repair and in pathologic states accompanied by neovascularization.
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PMID:Human keratinocytes express the three major splice forms of vascular endothelial growth factor. 779 44

Vascular endothelial growth factor (VEGF) is a secreted mitogen with high specificity toward endothelial cells. Expression of VEGF by smooth muscle cells in vivo may be an important stimulus for the regrowth of the endothelium after damage caused by interventions such as angioplasty. The levels of VEGF secreted by cultured smooth muscle cells minimally stimulated growth of endothelial cells in co-culture. Full length cDNA for the 165 amino acid residue, bovine VEGF (VEGF165), was isolated from calf liver total RNA by reverse transcriptase polymerase chain reaction (RT-PCR) techniques, and used to generate plasmid constructs for transfection. Bovine aortic smooth muscle cells (BSMC), stably transfected with VEGF165 plasmid DNA, secreted mitogen into conditioned culture medium at levels that are physiologically relevant (2-4 ng/ml). Transformed BSMC stimulated growth of bovine aortic endothelial cells (BAEC) in co-culture, to a significantly greater extent than mock transfected BSMC. Migration of BAEC was also enhanced by the presence of VEGF transduced BSMC. These data suggest that smooth muscle cells, genetically engineered to produce VEGF, may provide biologic linings in cardiovascular prostheses that could promote the growth of endogenous endothelial cells.
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PMID:Stimulation of growth and migration of vascular endothelial cells by vascular endothelial growth factor transduced smooth muscle cells in co-culture. 936 Jan 47

Vascular endothelial growth factor (VEGF)/vascular permeability factor is a likely angiogenic mediator in proliferative diabetic retinopathy, and its role is under scrutiny in the pathogenesis of the capillary leakage characteristic of background diabetic retinopathy. To examine whether the diabetic milieu induces or increases retinal VEGF expression in humans, we examined retinas from nondiabetic eye donors and donors with 9 +/- 5 years of diabetes and documented microangiopathy. To identify possible confounding effects of the postmortem period, we also studied the postmortem stability of the VEGF transcript and the expression of the VEGF protein in rat retinas. In both human and rat retina we detected by Northern analysis a 4.2-kb VEGF mRNA species and by reverse transcriptase polymerase chain reaction the transcripts encoding VEGF165 (the most abundant), VEGF121, and VEGF189. By in situ hybridization and immunohistochemistry VEGF mRNA and protein co-localized at the ganglion cell, inner nuclear, and outer plexiform layers and in the walls of the blood vessels (where mRNA was scarce). The protein was additionally detected in photoreceptors. The abundance and distribution of VEGF mRNA and protein were not altered in the diabetic retinas, indicating that the diabetic environment is not sufficient to increase retinal VEGF expression. The demonstration that VEGF is constitutively expressed in the adult retina and is localized to discrete neural cells and their processes proposes a role for the cytokine in retinal homeostasis and/or function.
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PMID:Expression of vascular endothelial growth factor in the human retina and in nonproliferative diabetic retinopathy. 962 50

We examined the expression of selected growth factors, growth factor receptors, elements of extracellular matrix and cell adhesion molecules in the germinal matrix layer (GML) utilizing immunohistochemistry and reverse transcriptase polymerase chain reaction. At autopsy brain samples from 10 neonatal infants were used. Epidermal growth factor receptor (EGFR) was significantly expressed in the matrix cells. While transforming growth factor alpha and heparin-binding epidermal growth factor-like growth factor were found in the matrix cells or vascular wall as ligands, epidermal growth factor was not expressed. EGFR and its ligands are thought to be important factors for the maintenance of the matrix cells and cell-to-cell interactions. Insulin like growth factor I, its receptor Ibeta and tenascin were found in the stroma of the GML and periventricular region. Vascular endothelial growth factor and receptor Flk-1, laminin A and B2, fibronectin, collagen type IV and integrins such as beta3, alpha5beta1 and alphaVbeta3 were found mainly in or around the vascular wall indicating their important roles for vascularization. Transforming growth factor beta2 and its receptor II were expressed in the matrix cells and/or vascular wall suggesting a role in proliferation and/or regression of the vasculature. CD44 and Thy-1 were also expressed in the matrix cells.
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PMID:Growth factors in infant germinal matrix: relationship to extracellular matrix and cell adhesion molecules. 973 49

Vascular endothelial growth factor is a potent direct-acting angiogenic factor. Early in hepatocarcinogenesis, hepatocellular carcinomas do not show hypervascularity; at later stages, they require abundant arterial blood flow. We investigated the role of vascular endothelial growth factor in hepatocellular carcinoma arterialization. We studied 51 patients with hepatocellular carcinoma. All patients had undergone hepatic arteriography. Vascular endothelial growth factor expression was investigated by immunohistochemistry (n = 51) and in situ hybridization (n = 13), and the changes in vascular endothelial growth factor expression were evaluated in relation to tumor differentiation and changes in tumor vascularity. The expression of vascular endothelial growth factor isoforms in hepatocellular carcinomas was also analyzed by reverse transcriptase-polymerase chain reaction (n = 10). Vascular endothelial growth factor expression was detected in hepatoma cells and hepatic stellate cells, and increased vascular endothelial growth factor expression was associated with tumor dedifferentiation. Vascular endothelial growth factor expression in hypervascular hepatocellular carcinomas was greater than in those not showing hypervascularity. The major vascular endothelial growth factor isoforms expressed in hepatocellular carcinoma were 121 and 165. These findings indicate that vascular endothelial growth factors 121 and 165 play a critical role in the process of angiogenesis in hepatocellular carcinomas.
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PMID:Increased expression of vascular endothelial growth factor is associated with tumor progression in hepatocellular carcinoma. 974 16

Vascular endothelial growth factor (VEGF) is a critical regulator of angiogenesis that stimulates proliferation, migration, and proteolytic activity of endothelial cells. Although the mitogenic activity of VEGF is endothelial cell specific, recent reports indicate VEGF is able to stimulate chemotaxis and tissue factor production in monocytes. VEGF-stimulated activity in monocytes is mediated by the VEGF receptor flt-1. The purpose of the present study was to investigate the effects of VEGF on another major cell type in the vascular wall, namely, the vascular smooth muscle cell (SMC). Using cultured cells, we showed that VEGF has a minimal mitogenic effect on SMCs, which is in accordance with published data. However, VEGF treatment significantly enhanced production of matrix metalloproteinase (MMP)-1, -3, and -9 by human SMCs. The upregulation of MMP-1 and MMP-9 was pronounced, and the stimulation for MMP-3 was less prominent. Stimulation could be demonstrated at both protein and mRNA levels, as reflected by ELISA, zymography, and Northern blot analysis. To explore the signal transduction pathway for the effect of VEGF on SMCs, we studied the expression of 2 high-affinity VEGF receptors, the kinase insert domain-containing receptor (KDR) and flt-1, in human SMCs. Both reverse transcriptase-polymerase chain reaction and immunoblotting revealed the expression of flt-1. Immunoprecipitation followed by immunoblotting illustrated phosphorylation of the flt-1 receptor after VEGF treatment. Similar methodology failed to detect expression of KDR in human SMCs. These data suggest the role of flt-1 in mediating VEGF-stimulated MMP expression of SMCs. The physiological relevance of MMP upregulation was studied by examining VEGF-stimulated SMC migration through 2 synthetic extracellular matrix barriers, Matrigel and Vitrogen. Our results indicate that VEGF treatment accelerated SMC migration through both barriers, and that this response was blocked by MMP inhibition in Matrigel, which supports a permissive role of MMP in SMC migration. These data are the first to show a direct effect of VEGF on SMCs. SMC-derived MMPs may be an additional source of proteases to digest vascular basement membrane, which is a crucial step in the initial stage of angiogenesis. The MMPs may also contribute to SMC migration in angiogenesis and atherogenesis.
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PMID:Vascular endothelial growth factor upregulates the expression of matrix metalloproteinases in vascular smooth muscle cells: role of flt-1. 977 30

Vascular endothelial growth factor (VEGF) has been identified as the substance that increases the permeability and proliferation of vascular endothelial cells. We examined the clinical significance of VEGF expression in 60 head and neck squamous cell carcinomas using the methods of Western blot, immunohistochemistry, and reverse transcriptase-polymerase chain reaction (RT-PCR), comparatively, and analysed the relationship between VEGF status in Western blot and tumour size, lymph-node status, histologic grade and disease-free survival (DFS) rate. Western blot analysis revealed high VEGF expressors (tumour/normal tissue density >/= 3-fold) in 26 patients (43%) and low VEGF expressors (< 3-fold) in 34 patients (57%). The results of the Western blot analysis correlated significantly with those of the RT-PCR (P = 0.00007) or immunohistochemistry (P = 0. 00006). High VEGF expressors are associated with the progression of lymph-node spread (P = 0.0009), which are correlated with poor DFS. The 2-year DFS rate of high VEGF expressors (30%) was significantly lower than that of low VEGF expressors (78%) (P = 0.0008). Multivariate analysis showed VEGF expression and stage were independent predictors for the DFS (P = 0.045 and 0.041, respectively). VEGF expression may play an important role in progression of HNSCC.
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PMID:Prognostic value of vascular endothelial growth factor (VEGF) in head and neck squamous cell carcinomas. 1095 83

Vascular endothelial growth factor-C (VEGF-C) functions specifically to induce lymphangiogenesis. We examined the relationship between expression of VEGF-C and clinicopathological features in patients with colorectal cancer. The expression of VEGF-C in the 99 primary tumours and 18 metastatic lymph nodes from colorectal cancer patients was examined immunohistochemically. To verify VEGF-C mRNA expression, reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out. The expression of VEGF-C correlated with lymphatic involvement, lymph nodes metastasis, and depth of invasion. On the other hand, correlations were nil with regard to gender of the patients, histologic type, venous involvement, and liver metastasis. The expression of VEGF-C in metastatic lymph nodes was fairly consistent with this expression in the primary tumour. Survival time was shorter for VEGF-C positive groups than for VEGF-C negative ones, but with no statistically significant difference. RT-PCR findings revealed that the expression of VEGF-C mRNA correlated mostly with that of VEGF-C protein expression. VEGF-C may play an important role in lymphatic spread of colorectal cancer.
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PMID:Vascular endothelial growth factor-C (VEGF-C) expression in human colorectal cancer tissues. 1097 Jun 90

Vascular endothelial growth factor (VEGF) is an angiogenic mitogen, specific for endothelial cells. Hypoxia-induced VEGF in endothelial cells and cardiomyocytes leads to autocrine and paracrine stimulation, respectively. During myocardial ischemia, VEGF is upregulated in the endothelium and myocardium, and may mediate angiogenesis. Morphine sulfate is commonly used in pain relief for patients with acute myocardial infarction. We investigated the effect of morphine sulfate on VEGF expression in cultured endothelial cells and cardiac myocytes subjected to hypoxia. Enzyme-linked immunosorbent assays showed that morphine sulfate significantly inhibited hypoxia-induced VEGF expression in mouse heart microvascular endothelial cells (SMHEC4), primary cultures of human umbilical vein endothelial cells (HUVECs) and in primary cultures of rat cardiac myocytes (P<0.05). Real time reverse transcriptase polymerase chain reaction showed that morphine treatment (100 ng/ml) of hypoxic HUVECs resulted in a significant reduction in mRNA levels of VEGF(121) and VEGF(165) isoforms. Transfection of HUVECs with a human VEGF promoter-luciferase construct showed that hypoxia-induced transcriptional activation of VEGF was markedly inhibited by morphine sulfate (P<0.05). Phosphatidyl inositol-3 kinase and protein kinase C-mediated activation of the VEGF promoter was also inhibited by morphine. The opioid antagonist naloxone significantly reversed the inhibitory effects of morphine in endothelial cells suggesting the involvement of opioid receptors. Our results show that the inhibitory effects of morphine on hypoxia-induced VEGF expression in endothelial cells and cardiac myocytes can lead to a decrease in the autocrine and paracrine stimulation and hence limit neovascularization of the ischemic myocardium.
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PMID:Morphine sulfate inhibits hypoxia-induced vascular endothelial growth factor expression in endothelial cells and cardiac myocytes. 1173 63

Vascular endothelial growth factor (VEGF) is a heparin-binding, dimeric polypeptide with potent mitogenic effects on endothelial cells. VEGF expression has also been reported in ovarian epithelial tumors (OETs), which may be associated with gonadotropin stimulatioin. We recently reported that most OETs, including OET cell lines, express gonadotropin receptors. Here we studied VEGF mRNA expression in 141 OET and 35 benign ovarian samples using reverse transcriptase polymerase chain reaction and in situ hybridization (ISH). We also studied VEGF production by OET cell lines under stimulation of gonadotropins. AO (serous carcinoma), low malignant potential (LMP; SV40-transformed borderline tumor) and ML-5 (SV40-transformed cystadenoma) cells were examined for VEGF protein production under the regulation of gonadotropins in vitro. The biologic function of VEGF was confirmed by using bovine endothelial growth assay. Whereas VEGF was not detected in benign ovarian surface epithelium or in ovarian epithelial inclusions, it was detected in both epithelial and stromal compartments of OETs. For VEGF epithelial expression, only 5% of ovarian cystadenomas and 30% of borderline tumors were positive for VEGF detection by ISH, whereas VEGF mRNA signal was detected in 80% of ovarian carcinoma cases. This increment of VEGF expression in ovarian carcinomas was statistically significant compared with benign and borderline tumors. Within ovarian carcinomas, the percentage of VEGF-positive cells was significantly associated with the grade of cancer but not with cancer cell types or cancer stages. Both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) stimulated the expression of VEFG(165) in AO cells in a dose-dependent manner. Maximal induction was obtained for FSH at dose of 40 mIU/ml and for LH at 50 mIU/ml after 48 hr of culture. Compared with the nonstimulated cells, VEGF level was significantly elevated in both LMP and AO cells after stimulation of gonadotropins. Furthermore, the induction of VEGF expression was significantly stronger in carcinoma cells than in borderline OET cells. These observations suggest that VEGF may play a role in the development of ovarian cancer and that the elevated gonadotropins, as found in menopause and in most ovarian cancer patients after surgery, could accelerate tumor growth and tumor recurrence by inducing VEGF expression in OETs.
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PMID:VEGF expression and enhanced production by gonadotropins in ovarian epithelial tumors. 1177 59


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