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

---

Query: EC:2.7.7.48 (transcriptase)
9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rat kidney proximal tubule epithelial cells (RPTE) in primary culture express acidic fibroblast growth factor 1 (FGF-1). Transformation of RPTE by SV40 (SV-RPTE) suppressed FGF-1 expression but activated secretion of FGF-like factor(s). SV-RPTE conditioned medium contained growth-promoting activity for SV-RPTE and human umbilical vein endothelial cells, indicating that both autocrine and angiogenic factors were secreted. Reverse transcriptase-polymerase chain reaction and Northern analysis for various FGFs showed that only FGF-3, also known as int-2, mRNA was expressed in SV-RPTE. In addition, expression of mRNA for the heparin-binding angiogenic factor vascular endothelial growth factor (VEGF) increased dramatically in SV-RPTE. Physical characterization of the activity in the SV-RPTE conditioned medium suggested that FGF-3 and VEGF contributed the autocrine and angiogenic activities, respectively. We also investigated FGF-3 and VEGF secretion in temperature-sensitive (ts) SV40-transformed RPTE. tsSV-RPTE had transformed properties resembling those of SV-RPTE only at the permissive temperature (33 degrees C), e.g., increased growth potential and anchorage-independent growth. FGF-1 was expressed only at the nonpermissive temperature. VEGF mRNA levels and secretion of the human umbilical vein endothelial cell growth-promoting activity were reduced by switching tsSV-RPTE cells from 33 degrees to 39 degrees C. However, FGF-3 mRNA levels were not affected significantly by the temperature switch suggesting that activation of VEGF and FGF-3 occurs through different mechanisms. These results indicate that FGF-1 expression in RPTE is suppressed by SV40 transformation.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Stable and temperature-sensitive transformation of rat kidney epithelial cells suppresses expression of acidic fibroblast growth factor 1 but activates secretion of fibroblast growth factor 3 (int-2) and vascular endothelial growth factor. 751 42

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen with potent angiogenic and vascular permeability-inducing properties, both of which may be important for the function of islets of Langerhans. In this study, we have examined the expression of VEGF and its tyrosine kinase receptors (flt and flk-1) in isolated rat islets of Langerhans in vitro. When analyzed by in situ hybridization, islet tissue showed a significant 4.6-fold increase in VEGF mRNA expression over time in culture from 0 to 7 days. Islet tissue exposed to hypoxic/anoxic conditions for a period of 8 hr showed a 3.7-fold increase in VEGF mRNA when analyzed by Northern blot hybridization. Reverse transcriptase-polymerase chain reaction revealed the presence of both flt and flk-1 in freshly isolated islets, and two VEGF isoforms, namely VEGF120 and VEGF164. Three rodent beta-cell lines derived from insulinomas (RINm5F-2A, INS-1, and MIN6) were also found to express VEGF by Northern blot hybridization. However, neither hypoxia/anoxia nor low (0.3 g/L)- or high (3.0 g/L)-glucose culture conditions modulated their expression of VEGF. VEGF derived from RINm5F-2A cells was bioactive in a three-dimensional in vitro model of angiogenesis, which assays for endothelial cell invasion and capillary morphogenesis. These findings demonstrate, first, that devascularization increases VEGF expression in isolated islet tissue, and they point to VEGF as a potentially important endogenous angiogenic stimulus for subsequent revascularization in vivo. Second, our observations raise the possibility that survival of transplanted islets may be improved by increasing VEGF expression before transplantation.
...
PMID:Vascular endothelial growth factor is increased in devascularized rat islets of Langerhans in vitro. 903 36

We investigated hormonal regulation of endometrial angiogenesis in menstruating primates. This study was designed to demonstrate: (i) that cell-specific vascular endothelial growth factor (VEGF) production and expression in monkey endometrium are regulated by steroid receptor ligands; and (ii) mifepristone (RU 486) alters VEGF production even in the absence of a progestin agonist. Endometrial VEGF production was compared by computer-assisted immunohistochemical analysis during induced hypoestrogenism and after oestradiol, progestin, or antiprogestin (mifepristone) treatment. VEGF gene expression was estimated by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) in endometrial samples from castrate cynomolgus monkeys, from intact monkeys in the luteal phase, and from monkeys treated for 20 days with levonorgestrel (LNG) or mifepristone. VEGF staining intensities in glandular epithelium and VEGF mRNA expression were highest in hypoestrogenic monkeys. Progestin treatment induced intense VEGF staining in the stroma. Gene expression of VEGF-189, but not other isoforms, was higher in progesterone- and progestin (LNG)-exposed endometria compared to mifepristone-exposed endometria or endometria from anovulatory cycles (P < 0.04). Mifepristone abolished VEGF staining in glandular epithelium almost completely. We conclude that VEGF protein and VEGF mRNA expression levels in primate endometrium depend on the steroidal milieu. Anti-angiogenic effects of mifepristone via suppression of VEGF production might represent a mechanism for its quelling effects on endometrium.
...
PMID:Vascular endothelial growth factor in primate endometrium is regulated by oestrogen-receptor and progesterone-receptor ligands in vivo. 922 18

Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis and is constitutively expressed in the synovium of rheumatoid arthritis (RA). Over-expression of VEGF may play an important role in pathogenic vascularization and synovial hyperplasia of RA. In the present study, we examined whether disease-modifying anti-rheumatic drugs (DMARDs), including bucillamine (BUC), gold sodium thiomalate (GST), methotrexate (MTX) and salazosulfapiridine (SASP), act by inhibiting the production of VEGF by cultured synovial cells of patients with RA. Treatment of cultured synoviocytes with lipopolysaccharide (LPS) significantly increased VEGF production by cultured synovial cells. BUC significantly inhibited LPS-induced VEGF production, while GST tended to inhibit the production of VEGF. The inhibitory effects on VEGF production were dose-dependent. In contrast, MTX and SASP did not affect VEGF production. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed that BUC also inhibited LPS-induced VEGF mRNA expression in RA synovial cells. The present study provides the first evidence that BUC inhibits VEGF production and the expression of its mRNA in synovial cells of RA patients. Our results indicate that the anti-rheumatic effects of BUC are mediated by suppression of angiogenesis and synovial proliferation in the RA synovium through the inhibition of VEGF production by synovial cells.
...
PMID:Inhibitory effects of anti-rheumatic drugs on vascular endothelial growth factor in cultured rheumatoid synovial cells. 1033 31

Primary effusion lymphomas (PELs), which are rare lymphomas associated with Kaposi's sarcoma-associated herpesvirus (or human herpesvirus-8) infection, present as malignant lymphomatous effusions in body cavities. Because PELs prefer liquid growth, we hypothesized that increased vascular permeability would be required for effusions to form. We found that the PEL cell lines BC-1, BCP-1, and BCBL-1 produce high levels of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF). Reverse transcriptase-polymerase chain reaction analysis of RNA from the PEL cell lines amplified the 3 VEGF-secreted isoforms: VEGF/VPF(121), VEGF/VPF(145), and VEGF/VPF(165). Two of the PEL cell lines expressed the VEGF/VPF receptor Flt-1, but VEGF/VPF did not stimulate proliferation in these cells. Most (13/14) control SCID/beige mice inoculated intraperitoneally with BCBL-1 cells and subsequently observed or treated with control antibodies developed effusion lymphoma of human cell origin with prominent bloody ascites. In contrast, none (0/9) of the mice treated with a neutralizing antihuman VEGF/VPF antibody developed ascites and effusion lymphoma. These results demonstrate that VEGF/VPF is critical to BCBL-1 growth as effusion lymphoma in mice and suggest that VEGF/VPF stimulation of vascular permeability may be critical to the pathogenesis of PELs.
...
PMID:Role of vascular endothelial growth factor/vascular permeability factor in the pathogenesis of Kaposi's sarcoma-associated herpesvirus-infected primary effusion lymphomas. 1059 69

Because the crucial role of angiogenesis has been demonstrated in tumor growth and metastasis, the present study was undertaken to characterize the relative expression of vascular endothelial growth factors VEGF (vascular endothelial growth factor), VEGF-B, VEGF-C, and their receptors KDR (kinase insert domain-containing receptor), FLT-1 (fms-like tyrosine kinase), and FLT-4 in human colonic cancers, in relation to the Astler-Coller pathological classification, and to prognosis. VEGF and VEGF-B gene expression was quantified by Northern blot in 72 tumor samples matched with control tissues. VEGF gene expression was 1.4 times higher in adenocarcinomas than in control tissues (p = 0.02), but did not increase further between Astler-Coller tumor stages A and D, and did not correlate with disease recurrence for patients at stages B2 or C. In adenomas, VEGF mRNA levels were not significantly different from those in the paired control colonic mucosa. The expression pattern of VEGF isoforms, mainly identified by RT-PCR (reverse-transcriptase-coupled polymerase chain reaction) as VEGF121 and VEGF165 and to a lesser extent VEGF189, was comparable in tumor and control tissues. VEGF-B mRNA levels were unchanged during the neoplastic progression of colonic mucosa. In contrast to KDR and FLT-4, the expression of VEGF-C and FLT-1 genes increased in some pathological tissues. These results provide evidence that the early and sustained increase in VEGF transcripts and the expression of multiple angiogenic factors and receptors contribute to the development of colon cancer, and thus constitute a putative target for anti-angiogenic drug therapy.
...
PMID:Vegf, Vegf-B, Vegf-C and their receptors KDR, FLT-1 and FLT-4 during the neoplastic progression of human colonic mucosa. 1073 43

In the initial phase of wound healing, endogenous fibrin clots are known to form a provisional matrix and to promote angiogenesis. Growth factors such as vascular endothelial growth factor (VEGF) increase in wounds to stimulate angiogenesis. However, it remains unknown whether VEGF is induced when fibrin is used as a dermal substrate for cultured skin substitutes. The authors investigated the effect of fibrin gel as a dermal substrate for a cultured skin substitute, using human keratinocytes and dermal fibroblasts. A collagen-cultured skin substitute was also examined for comparison. VEGF in the culture supernatant in both types was measured by enzyme-linked immunosorbent assay, and VEGF mRNA was determined semiquantitatively by reverse-transcriptase polymerase chain reaction after 2 days of incubation. Experiments were performed using 12 cultured skin substitutes: four for histologic examination before transplantation, four for VEGF assay in vitro, and four for the transplantation to athymic mice. Three independent experiments were performed for each step. VEGF concentration in the fibrin-cultured supernatant was 84.3 +/- 11.8 pg/ml, whereas it was 27.8 +/- 4.68 pg/ml in the case of the collagen substrate. The relative levels of VEGF mRNA were 1.088 +/- 0.100 and 0.698 +/- 0.226, respectively. In in vivo transplantation, the fibrin-type cultured skin substitute showed an excellent take on the wound bed, and a normally proliferating keratinocyte layer with emergence of vascular endothelial cells in the transplanted floor was seen 3 days after transplantation. Vascular endothelial cells, which were identified using alkaline phosphatase stain, were significantly increased in the fibrin-type cultured skin substitute. The use of fibrin as a dermal substrate for cultured skin substitute increases the secretion of VEGF, improves regeneration of mature epidermal structure after in vivo transplantation, and promotes the migration of vascular endothelial cells.
...
PMID:Induction of vascular endothelial growth factor by fibrin as a dermal substrate for cultured skin substitute. 1265 9

Angiogenesis or new vessel formation is an essential component in the growth and progression of neoplasms and there is growing evidence of its importance in hematological malignancies including multiple myeloma (MM). Vascular endothelial growth factor (VEGF) is believed to play a role in tumor angiogenesis. We studied the expression of VEGF and its receptors (VEGFR1 or Flt-1 and VEGFR2 or Flk-1/KDR) by myeloma cell lines and plasma cells isolated from patients, using different methods. VEGF expression by the plasma cells was demonstrated by immunohistochemistry in 18 of 20 patients with MM. Enzyme-linked immunosorbent assay demonstrated VEGF secretion in all six different myeloma cell lines studied. Five patient marrow samples and seven different myeloma cell lines were then studied for VEGF mRNA expression by reverse-transcriptase polymerase chain reaction (RT-PCR), which was positive in all. We further evaluated the expression of both VEGFR1 and VEGFR2 in different myeloma cell lines and five sorted myeloma bone marrow samples by RT-PCR. All the myeloma cell lines expressed VEGFR1 and three of the cell lines expressed VEGFR2. VEGFR1 expression was detected in all and VEGFR2 in all but one of the sorted marrow samples. Increased expression of VEGF by the myeloma cells taken in the context of the suspected prognostic value of marrow angiogenesis suggests a pathogenetic role for this cytokine and presence of its receptors on myeloma cells points toward an autocrine mechanism. Demonstration of the presence of VEGFR2 in our study provides a potential biological explanation for the preclinical activity observed with VEGFR2 inhibitors.
...
PMID:Expression of VEGF and its receptors by myeloma cells. 1451 53

Vascular endothelial growth factor (VEGF) enhances the permeability of blood vessels, which is an important vascular change observed during inflammatory processes. The purpose of this in vitro study was to investigate the effect of proinflammatory cytokines on the expression of VEGF mRNA gene in human pulp and gingival fibroblasts. Interlukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF-alpha) were used to evaluate VEGF mRNA gene expression in human pulp and gingival fibroblasts. The levels of mRNAs were measured by quantitative reverse-transcriptase polymerase chain reaction analysis. Both IL-1alpha and TNF-alpha induced significantly high levels of VEGF mRNA gene expression in human pulp and gingival fibroblasts (p < 0.05). In addition, TNF-alpha was found to be more effective in the induction of VEGF mRNA gene expression in pulp than gingival fibroblasts (p < 0.05). Moreover, IL-1alpha was found to be more effective in the induction of VEGF mRNA gene expression than TNF-alpha in gingival fibroblast cultures (p < 0.05). These results indicate that proinflammatory cytokines can induce VEGF mRNA gene expression, and such an effect may partially contribute to the destruction of pulpal and periapical tissues through promoting expansion of the vascular network coincident to progression of the inflammation.
...
PMID:Induction of vascular endothelial growth factor gene expression by proinflammatory cytokines in human pulp and gingival fibroblasts. 1544 63

Vascular endothelial growth factor (VEGF) is a regulator of angiogenesis, vasculogenesis, and vascular permeability. Recent reports suggest that VEGF may play a critical role in formation of peritumoral brain edema (PTBE) associated with meningiomas. While VEGF expression has been shown in meningiomas, studies have not focused on VEGF in the adjacent peritumoral brain regions. The present study examined the protein and gene expression of VEGF in human meningiomas and peritumoral brain areas. Biopsies were obtained from 37 patients. Immunohistochemical staining and immunoblotting were performed to detect the expression of VEGF protein. Reverse-transcriptase polymerase chain reaction (RT-PCR) was used to analyze the presence and quantity of VEGF mRNA. The extent of PTBE was estimated as an edema index (EI) based on preoperative magnetic resonance imaging. In meningiomas, western blot and RT-PCR results were congruent and the expression of both protein and mRNA had a significant correlation with EI. However, in peritumoral areas, western blot results were not consistent with the RT-PCR results. Protein results showed high correlation with EI, but mRNA was almost undetectable. In VEGF-positive cases, a decreasing gradient of VEGF protein expression was observed with increasing distance from tumors. These data suggest that peritumoral tissue does not produce VEGF and that VEGF protein levels in peritumoral tissues have a high correlation with EI. We conclude that VEGF macromolecules are secreted by the tumor tissue and enter peritumoral normal brain tissue to induce edema.
...
PMID:Expression of vascular endothelial growth factor in human meningiomas and peritumoral brain areas. 1898 27


1 2 Next >>

---