Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The distribution of myeloid lineage-associated cytokine receptors and lysosomal proteins was analyzed in human CD34+ cord blood cell (CB) subsets at different stages of myeloid commitment by reverse-transcriptase polymerase chain reaction (RT-PCR). The highly specific granulomonocyte-associated lysosomal proteins myeloperoxidase (MPO) and lysozyme (LZ), as well as the transcription factor PU.1, were already detectable in the most immature CD34+Thy-1+ subset. Messenger RNA (mRNA) levels for the granulocyte-colony stimulating factor (G-CSF) receptor, granulocyte-macrophage (GM)-CSF receptor alpha subunit and tumor necrosis factor (TNF) receptors I (p55) and II (p75) were also detected in this subset in addition to c-kit and flt-3, receptors known to be expressed on progenitor cells. By contrast, the monocyte-macrophage colony stimulating factor (M-CSF) receptor was largely absent at this stage and in the CD34+Thy-1-CD45RA- subsets. The M-CSF receptor was first detectable in the myeloid-committed CD34+Thy-l-CD45RA+ subset. All other molecules studied were found to be expressed at this stage of differentiation. Different cocktails of the identified ligands were added to sorted CD34+Thy-1+ single cells. Low proliferative capacity was observed after 1 week in culture in the presence of stem cell factor (SCF) + Flt-3 ligand (FL) + G-CSF. Addition of GM-CSF to this basic cocktail consistently increased the clonogenic capacity of single CD34+Thy-1+ cells, and this effect was further enhanced (up to 72.3 +/- 4.3% on day 7) by the inclusion of TNF-alpha. In conclusion, the presence of myeloid-associated growth factor receptor transcripts in CD34+ CB subsets does not discriminate the various stages of differentiation, with the exception of the M-CSF receptor. In addition, we show that TNF-alpha is a potent costimulatory factor of the very immature CD34+Thy-1+ CB subset.
 ...
PMID:Analysis of myeloid-associated genes in human hematopoietic progenitor cells. 932 52

The pituitary gland, a highly vascularised endocrine organ, contains permeable fenestrated endothelium that allows direct access of endocrine cells to the hemal milieu. Vascular endothelial growth factor (VEGF) has a mitogenic effect on endothelial cells and renders the endothelium more permeable. The following study investigated the expression of VEGF and its receptor flt-1 mRNA and protein in the pituitary gland of sheep. VEGF expression was localised, by in situ hybridisation and immunocytochemistry, mainly to the pars tuberalis/zona tuberalis (PT/ZT) region of the gland. No hybridisation signal was observed in the pars intermedia or pars nervosa. Reverse transcriptase-polymerase chain reaction (RT-PCR) Southern blotting confirmed the predominant expression of VEGF in the PT/ZT compared with the pars distalis (PD). Western blot analysis with the VEGF antibody revealed major (48 kDa) and minor (24 kDa) bands representing the monomer and dimer forms of VEGF and also confirmed the differential expression of VEGF in the PT/ZT compared with the PD. Double immunocytochemistry with VEGF and prolactin or luteinising hormone-beta (LH-beta) antibodies demonstrated that the VEGF-secreting cells are not lactotrophs or gonadotrophs. However, co-localisation of VEGF with S-100 was observed in a proportion of cells suggesting that some VEGF secreting cells are follicular stellate. Immunocytochemistry with a flt-1 antibody confirmed the expression of this high affinity receptor for VEGF in endothelial cells across the pituitary gland. Immunocytochemistry with the VEGF antibody using pituitary glands from intact and hypothalamo-pituitary disconnected sheep demonstrated comparable expression patterns suggesting that the regulation of blood flow and vascular permeability in the pituitary gland is under local regulation and is independent of hypothalamic input.
 ...
PMID:Pattern and localisation of expression of vascular endothelial growth factor and its receptor flt-1 in the ovine pituitary gland: expression is independent of hypothalamic control. 942 52

VEGF (vascular endothelial growth factor) is a multifunctional cytokine active on blood vessel cells. The present study measured VEGF in the aqueous phase of human milk and examined how the concentration varied with gestational age and the duration of lactation after birth. We hypothesized that VEGF-specific receptors were present on the apical surface of intestinal epithelial cells. The concentration of monomeric VEGF (containing 165 residues) measured by ELISA in the breast milk was 2 orders of magnitude greater than that measured in the serum of normal adults. The VEGF165 concentration in the first week of lactation was greater in the breast milk of mothers of full-term than in preterm babies (p < 0.05). The concentration in the breast milk of mothers of full-term infants decreased (p < 0.01) after the first week of lactation. Scatchard analysis of radioligand-receptor binding showed the presence of specific receptors for 125I-VEGF165 on the surface of Caco-2, an intestinal epithelial cell line, with a kd of 2.85 to 4 nM. Reverse transcriptase PCR of Caco-2 cell RNA showed mRNA for the VEGF receptor flt-1. In conclusion, VEGF is present in high concentrations in breast milk and binds to specific receptors on cells derived from intestinal epithelium.
 ...
PMID:Vascular endothelial growth factor (VEGF) is present in human breast milk and its receptor is present on intestinal epithelial cells. 1023 59

Angiogenesis is a complex process that includes recruitment and proliferation of mural cells-smooth muscle cells (SMC) and pericytes. Vascular endothelial growth factor (VEGF) has been shown to play an important role in angiogenesis and is an endothelial cell chemoattractant. In addition, certain VEGF isoforms have been implicated in the normal formation of smooth muscle cell-surrounded arteries. Because VEGF's role as a mural cell chemoattractant had not been explored, we examined the ability of VEGF to influence vascular SMC migration in vitro. A Boyden chamber migration assay demonstrated that VEGF (0-100 ng/ml) caused a dose-dependent migration of SMC. VEGF did not cause proliferation of SMC. Reverse transcriptase-polymerase chain reaction analysis demonstrated the presence of both KDR and flt mRNA, two known VEGF receptors, in SMC cultures. Western blot analysis of SMC lysates confirmed these data, revealing bands migrating at approximately 200 kDa and slightly below 200 kDa consistent with KDR and flt. These observations demonstrate that VEGF receptors are present on SMC, and that VEGF can act as an SMC chemoattractant.
 ...
PMID:Vascular endothelial growth factor-induced migration of vascular smooth muscle cells in vitro. 1045 28

The Achilles tendon is one of the most common sites of injury and rupture. Evidence suggests that local vascularisation is involved in this aetiology. We investigated the expression of one important angiogenic factor, the vascular endothelial growth factor (VEGF), in normal and pathologic human Achilles tendons using immunohistochemical, biochemical, molecular and cell biology methods. VEGF could be immunostained in tenocytes of ruptured and foetal Achilles tendons, but not in normal adult ones. In microvessels, the VEGF receptor VEGFR-1 (flt-1) could be visualised as well. High VEGF levels were measured in homogenates from ruptured adult, lower ones in foetal and negligible concentrations in normal adult Achilles tendons using enzyme-linked immunoassay (ELISA) and Western blot experiments. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed that the splice variants VEGF121 and VEGF165 are exclusively expressed. In tenocytes cultivated from newborn rat Achilles tendons, hypoxia or epidermal growth factor (EGF) raised VEGF production moderately whereas their combination resulted in a strong, synergistic induction. These results prove the presence of an angiogenic peptide and vascularisation in ruptured and foetal tendons and support the view that microtrauma or degeneration in the Achilles tendon precedes its rupture.
 ...
PMID:The angiogenic peptide vascular endothelial growth factor is expressed in foetal and ruptured tendons. 1171 Jun 46

The mucosal cells were isolated from the ampullary regions of 20 human oviducts and cultured with or without hCG in five different concentrations (1-100 ng/mL). As analyzed by the semiquantitative reverse-transcriptase polymerase chain reaction, hCG treatment significantly increased mRNA expression of vascular endothelial growth factor and its receptor flt-1 in the cultured mucosal cells in a dose-dependent manner but had no effect on the expression of another receptor, KDR.
 ...
PMID:Upregulation of mRNA expression of vascular endothelial growth factor and its receptors by exogenous human chorionic gonadotropin in cultured oviduct mucosal cells. 1558 89