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Results for “Becaplermin”

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At least 145 records · Page 8Linked to original sources
PubMed1994

Platelet-derived growth factor is a potent stimulator of expression of intercellular adhesion molecule-1 in human arterial smooth muscle cells.

The effects of platelet-derived growth factor (PDGF) on the expression of intercellular adhesion molecule-1 (ICAM-1) as an indicator of cell activation were investigated in cultured human arterial smooth muscle cells (SMC). PDGF-BB and -AB but not -AA at 2-10 ng/ml stimulated ICAM-1 expression at a subconfluent but not a confluent state in a dose-dependent manner. ICAM-1 expression was induced at 2h, reached a plateau at 4h, and continued for at least 24h after stimulation with PDGF. The maximal stimulatory effect of PDGF-BB at 10 ng/ml was comparable to that by optimal concentrations of other cytokines and inflammatory agents. These data suggested that PDGF was a potent stimulator of ICAM-1.

Antigens, CD↗
PubMed1994

Translation initiation from non-AUG codons in COS1 cells is mRNA species dependent.

Sendai virus P/C mRNA, human erythrocyte membrane protein 4.1 mRNA and PDGF-B chain mRNA were used to test whether translation initiation from non-AUG codons in COS1 cells was mRNA species dependent. Site-directed mutants of the authentic translation start sites of these mRNAs to alternate start codons showed that while P/C mRNA is capable of initiating translation from non-AUG start sites the other two mRNAs are not. Our study shows that translation initiation from non-AUG codons is mRNA species dependent and suggests that higher order structure of an mRNA determines the non-AUG translation start site.

Animals↗
PubMed1994

Mitogenic signals control translation of the early growth response gene-1 in myogenic cells.

Muscle is a major site of expression of the early growth response gene-1 (Egr-1). To investigate its role in muscle proliferation and/or differentiation we studied the effect of a variety of growth factors on cultured mouse muscle Sol8 cells. Three groups of responses could be distinguished: 1. AII, endothelin, phenylephrine, and PMA induced Egr-1 mRNA accumulation, but the message remained untranslated. These factors induced neither differentiation nor proliferation. 2. Insulin induced differentiation. It stimulated Egr-1 mRNA accumulation, but no translation into the Egr-1 protein was seen. 3. bFGF, PDGF BB, and FCS strongly induced DNA- and protein synthesis (i.e. proliferation) and Egr-1 mRNA accumulation. Only under these conditions was the message translated into protein. We conclude: 1. AII, endothelin, phenylephrine, and PMA elicit a nuclear response in Sol8 muscle cells which may lead to reprogramming of genes unrelated to differentiation or proliferation. 2. Differentiation induces a translational block of the Egr-1 mRNA which is only relieved by mitotic stimuli. 3. These results strongly suggest a pivotal role of Egr-1 in muscle proliferation and define translational control as a new mechanism of Egr-1 regulation.

Angiotensin II↗
PubMed1994

Participation of diacylglycerol kinase in mitogenic signal transduction induced by platelet-derived growth factor in vascular smooth muscle cells.

In rat vascular smooth muscle cells, platelet-derived growth factor (PDGF), stimulated phosphatidic acid synthesis by activating both of the two alternative pathways, diacyglycerol kinase (DGK) and phospholipase D (PLD). Genistein, a tyrosine kinase inhibitor, inhibited PLD activation but not DGK activation, the latter was inhibited selectively by R 59022. PDGF-induced DNA synthesis was partially inhibited by genistein or R 59022, but these inhibitors had no effect on phorbol ester-induced DNA synthesis. Further, the specific effects of these inhibitors on PDGF-induced DNA synthesis were additive.

Alkaloids↗
PubMed1995

Hypoxia-induced transcription of the vascular endothelial growth factor gene is independent of functional AP-1 transcription factor.

In this study, we investigated the functional role of the transcription factor AP-1 in hypoxia-induced expression of the vascular endothelial growth factor (VEGF) by using dexamethasone as an inhibitor of AP-1 activity. Phorbol ester and platelet-derived growth factor (PDGF) cause an increase in VEGF mRNA expression, which is strongly suppressed in the presence of dexamethasone, whereas hypoxia-induced VEGF expression is not inhibited by dexamethasone. Studies using a VEGF promoter luciferase construct show that the phorbol ester and PDGF-induced VEGF expression is mediated at least in part by transcriptional activation of the VEGF promoter, whereas no transcriptional activation is seen under hypoxic conditions. In contrast, hypoxia leads to an increase in VEGF mRNA stability, as confirmed by experiments using actinomycin D as an inhibitor of transcription. These results indicate that hypoxia-induced VEGF expression is independent of AP-1 mediated transcription.

3T3 Cells↗
PubMed1995

Platelet-derived growth factor isoforms PDGF-AA, -AB and -BB exert specific effects on collagen gene expression and mitotic activity of cultured human wound fibroblasts.

This study was designed to clarify the action of three different isoforms of PDGF (PDGF-AA, PDGF-AB and PDGF-BB) on the proliferation rate and collagen synthesis of fibroblasts cultured from normal human wounds. PDGF-AA and PDGF-BB down-regulated both the steady-state levels of pro alpha 1 (I) and pro alpha 1 (III) collagen chain mRNAs and the production of collagen, both in a dose-dependent manner. Interestingly, low concentrations (1 ng/ml) of PDGF-AB up-regulated the expression of type I and III procollagen mRNAs by cultured wound fibroblasts, while under high concentrations (30 ng/ml) of PDGF-AB this effect changed to the opposite. The proliferation rate of wound fibroblasts was stimulated by PDGF-BB which elicited a dose-dependent (1-30 ng/ml) stimulation of cell proliferation, whereas PDGF-AB and -AA were less effective in this respect.

Becaplermin↗
PubMed1995

High D-glucose stimulates the cell cycle from the G1 to the S and M phases, but has no competent effect on the G0 phase, in vascular smooth muscle cells.

The effects of high (28mM) D-glucose (HG) on the cell cycle progression were investigated in rat aorta vascular smooth muscle cells (VSMCs) in primary culture, using an immunocytochemical analysis of cell-cycle-specific nuclear antigens. HG had no effect on the cell cycle of the serum-deprived G0 cells, whereas platelet-derived growth factor (PDGF) stimulated the entry of the G0 cells to the G1 phase without a further progression to the S and M phases. HG, but neither mannitol nor L-glucose, stimulated the progression of the PDGF-pretreated G1 cells to the S and M phases, which was blocked by calphostin-C, a protein kinase C (PKC) blocker. HG did not affect the cytosolic Ca2+ concentration ([Ca2+]i). These data suggest that HG has no competent effect on the G0 cells and acts as a progression growth factor (to stimulate the cell cycle from the G1 to the S/M) in VSMCs through the mechanism, which may be insensitive to [Ca2+]i and mediated by PKC.

Animals↗
PubMed1995

Ligand-induced polyubiquitination of receptor tyrosine kinases.

The platelet-derived growth factor beta-receptor undergoes polyubiquitination as a consequence of ligand binding. In the present study, we have examined the ligand-induced receptor ubiquitination also in the other receptor tyrosine kinase (structurally different) subfamilies by immunoblotting with anti-ubiquitin antiserum. In addition to the platelet-derived growth factor alpha- and beta-receptors, all the monomeric receptor tyrosine kinases examined, such as the receptors for epidermal growth factor (subfamily I), colony stimulating factor-1 (subfamily III), and fibroblast growth factor (subfamily IV), were found to be ubiquitinated after ligand stimulation. However, the insulin receptor (subfamily II), which is a tetrameric molecule, was not. These data suggest that the ligand-induced polyubiquitination of the receptor is a general phenomenon observed in most of the monomeric receptor tyrosine kinases.

3T3 Cells↗
PubMed1996

The novel regulatory mechanism of Fas system-mediated apoptosis in mesangial cells: implication to mesangial proliferative glomerulonephritis.

Fas Ag is a cell surface molecule that transduces the signal for apoptosis. Since mesangial cells (MC) play important roles in regulating glomerulonephritis, we investigated regulatory mechanisms of Fas system in MC. Fas Ag was expressed on MC from normal mice. This Fas Ag expression was down-regulated by inducing proliferation with platelet-derived growth factor or 18% fetal bovine serum, but was reversed when cycloheximide was added to the culture. Anti-Fas Ab alone did not induce apoptosis in MC, but MC became susceptible to apoptosis induced by anti-Fas Ab is actinomycin D or cycloheximide was added. Noteworthy findings are that mRNA of Fas ligand was expressed in MC. Taken together, MC appears to control the proliferation by regulating Fas system-mediated apoptosis, at least in part, through an autoregulatory mechanism with Fas Ag Fas ligand expressed on their own MC.

Animals↗
PubMed1996

Differential labelings suggest two specific phospholipid subclass hydrolysis promoted by PDGF-BB in vascular smooth muscle cells.

We have used differential phospholipid subclass labelings performed with [3H]lyso PAF and [3H] myristic acid into vascular smooth muscle cells (vSMC) to characterize the subclasses of phospholipid substrates upon different stimulation times with platelet-derived growth factor (PDGF-BB). In cells labeled with [3H]lyso PAF, PDGF-BB induced a sustained hydrolysis of alkyl-PE. In contrast, in [3H]myristic acid-labeled cells, PDGF-BB promoted a rapid and transitory hydrolysis of diacyl-PC. This hydrolysis was concomitant with an synthesis of diglyceride (DG) and phosphatidic acid (PA). Thus, both diacyl-PC and alkyl-PE appear to be major targets in PDGF-BB stimulation of SMC. These results suggest that agonists could induce the hydrolysis of precise phospholipid subclasses leading to a new specificity into the signal transduction cascade.

Animals↗
PubMed1996

P2U purinergic activation leads to the cell cycle progression from the G1 to the S and M phases but not from the G0 to G1 phase in vascular smooth muscle cells in primary culture.

The regulation of the cell cycle by extracellular UTP was investigated in rat aortic smooth muscle cells in primary culture (VSMCs) by means of an immunocytochemical analysis of cell cycle-specific nuclear antigens. UTP induced a rise in the cytosolic Ca2+ concentration ([Ca2+]i) of VSMCs, which was desensitized by pretreatment with ATP, but not with 2-methylthioATP nor alpha, beta-methyleneATP. The incubation of serum-deprived G0 cells with platelet derived growth factor (PDGF) induced cell cycle progression into the G1 phase without any further progression into the S and M phases, while none of the nucleotides had any effect on the cell cycle of the G0 cells. The incubation of the PDGF-pretreated cells at the G1 phase with 2-methylthioATP or alpha, beta-methyleneATP had no effect on the cell cycle of G1 cells, while the incubation of the G1 cells with UTP, ATP, and ATP gamma S stimulated cell cycle progression into the S and M phases. These results thus indicate that P2U purinergic activation mediates a [Ca2+]i transient and a progression growth factor effect of nucleotides in VSMCs.

Adenosine Triphosphate↗
PubMed1996

Advanced glycation endproducts-receptor interactions stimulate the growth of human pancreatic cancer cells through the induction of platelet-derived growth factor-B.

The molecular basis for the clinical association between diabetes mellitus and pancreatic cancer was investigated, using Mia PaCa-2 human pancreatic cancer cells in culture. Advanced glycation endproducts (AGE) prepared with bovine serum albumin and glucose were found to stimulate Mia PaCa-2 cell synthesis of DNA in a dose-dependent manner and also to significantly increase the number of viable cells. Evidence that platelet-derived growth factor-B (PDGF-B) mediates this growth promotion was obtained; AGE upregulated the level of PDGF-B mRNA, and antibodies against PDGF-BB completely neutralized the AGE-induced DNA synthesis. Antisense oligodeoxyribonucleotides complementary to mRNA encoding a receptor for AGE were found to reverse both the PDGF-B upregulation and the AGE-induced DNA synthesis. These results thus indicate that AGE ligand-receptor interactions could play an active part in the progression of pancreatic cancer through the induction of autocrine PDGF-B.

Base Sequence↗
PubMed1996

Platelet-derived growth factor B-chain homodimer suppressing a convulsion of epilepsy model mouse El.

El mouse is a mutant which has epileptic convulsions after tossing-up stimulations and has a hippocampal dysfunction. Platelet-derived growth factor B-chain homodimer has been reported to be a trophic factor of hippocampal neurons. We found that a recombinant PDGF-BB suppressed the convulsions of El mice in a dose-dependent manner. Furthermore, thrombin-treated mice manifested no convulsions, but thrombin receptor activating peptide-treated ones had convulsions. These findings suggest that an abnormality in PDGF-BB release may make El mice susceptible to tonic-clonic convulsions.

Animals↗
PubMed1996

Phosphatidylinositol 3-kinase activity is required for the activation process of focal adhesion kinase by platelet-derived growth factor.

Platelet-derived growth factor (PDGF) is one of the agents which stimulate increase in phosphotyrosine content of focal adhesion kinase (FAK) in cultured cells. In the present study we report that wortmannin, a highly specific and potent inhibitor of the catalytic subunit of mammalian phosphatidylinositol (PI) 3-kinase, completely abolishes PDGF-BB-mediated increase in tyrosine phosphorylation of FAK in human umbilical vein smooth muscle cells. Furthermore, analysis of the wild-type and mutant human PDGF beta-receptors stably expressed in porcine aortic endothelial cells also demonstrates that the Y740/751F mutant receptor, which cannot interact with PI 3-kinase due to the mutational alteration of its binding sites for PI 3-kinase, fails to increase FAK phosphorylation after PDGF-BB stimulation. These data suggest the requirement for PI 3-kinase activity in the activation process of FAK downstream of the PDGF receptor.

Androstadienes↗
PubMed1996

A possible mechanism for the stimulation of metalloproteinase production in human aortic intimal smooth muscle cells by linoleic acid hydroperoxide.

To approach the mechanism of the stimulating effect of linoleic acid hydroperoxide on the production of matrix metalloproteinases (MMPs) in human aortic intimal smooth muscle cells (ISMC), we investigated the effect of the hydroperoxide on the cytosolic level of Ca2+. Linoleic acid hydroperoxide provoked an increase in the cytosolic Ca2+ level, but it had no effect on the level of inositol phosphates (IPs) in these cells, in contrast with the effect of platelet-derived growth factor (PDGF), which elevated the level of both Ca2+ and IPs in these cells. A23187, a calcium ionophore, stimulated ISMC to produce matrix prometalloproteinase 1. These results indicate that linoleic acid hydroperoxide stimulates the production of MMPs in ISMC by elevation of the cytosolic Ca2+ level without the intervention of IPs. In addition, we found that the hydroperoxide has no effect on the binding of PDGF to its specific receptor on ISMC.

Aorta, Thoracic↗
PubMed1996

Activation of Na+/H+ exchanger is not involved in the PDGF-BB-induced DNA-synthesis in vascular smooth muscle cells.

HOE 694 [(3-methylsulphonyl-4-piperidinobenzoyl)guanidine methanesulphonate] was characterized as a new, potent, non-amiloride inhibitor of the Na+/H+ exchanger. In order to elucidate whether the Na+/H+ exchanger isoform 1 (NHE-1) is involved in the PDGF-BB-induced DNA-synthesis in vascular smooth muscle cells, we investigated the effect of HOE 694 and EIPA on the PDGF-BB-induced DNA synthesis. EIPA (10 microM) inhibited the PDGF-BB-induced stimulation of the Na+/H+ exchanger and the PDGF-BB-induced DNA synthesis in a concentration-dependent manner. HOE 694 (1-50 microM) dose-dependently inhibited the PDGF-BB-induced stimulation of the Na+/H+ exchanger but had no significant effects on DNA-synthesis. Our findings suggest that activation of the Na+/H+ exchanger is not essential for PDGF-BB-induced vascular smooth muscle cell growth.

Amiloride↗
PubMed1997

Regulation by cAMP of STAT1 activation in hepatic stellate cells.

Previously we reported that dibutyryl cAMP and phosphodiesterase inhibitor methylxanthines block rat stellate cell proliferation. To analyze the underlying mechanism, modulation by these agents of platelet-derived growth factor (PDGF)/BB-stimulating signal pathway was studied. Without reducing STAT1 protein level, these agents were found to attenuate STAT1 activation in stellate cells stimulated with PDGF/BB as revealed by an electrophoretic mobility shift assay. Inhibitory effect started 12 h after exposure of the cells to these agents at concentrations of more than 100 microM. These agents had no effects on DNA binding activity of STAT1 that had already been activated. Treatment with these agents failed to affect the function of PDGF receptors except for partial attenuation of phospholipase C activation under PDGF/BB stimulation. The present results indicate that inhibition of STAT1 activation may be one of factors involved in the cAMP-dependent stellate cell growth arrest.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Endothelial nitric oxide synthase gene transfer inhibits platelet-derived growth factor-BB stimulated focal adhesion kinase and paxillin phosphorylation in vascular smooth muscle cells.

Stimulation of smooth muscle (VSM) cells of guinea pig coronary artery by platelet-derived growth factor (PDGF)-BB retards paxillin mobility (mobility shift) in SDS-PAGE in a time-dependent manner. This mobility shift may be due to tyrosine phosphorylation of paxillin. eNOS gene transfer by replication deficient recombinant adenovirus vector AD5/RSVeNOS in VSM cells inhibited PDGF-BB-stimulated mobility shift and tyrosine phosphorylation of paxillin. Concomitantly, tyrosine phosphorylation of focal adhesion kinase (FAK) was also inhibited. The inhibition of paxillin and FAK tyrosine phosphorylation did not affect stress fiber and focal adhesion formation. Considering the importance of FAK and paxillin in cell migration and proliferation, these results suggest that the FAK-paxillin pathway is a target for NO action to inhibit VSM cell migration and proliferation.

Animals↗