Epidermal Growth Factor Upregulates Aminopeptidase N and 5′–Nucleotidase in Human Glomerular Mesangial Cells

1998 ◽  
Vol 21 (5) ◽  
pp. 310-316 ◽  
Author(s):  
Vladisav Stefanovi´c ◽  
Predrag Vlahovi´c ◽  
Marina Miti´c-Zlatkovi´c
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Mesangial Cells ◽  
Aminopeptidase N ◽  
Glomerular Mesangial Cells ◽  
Epidermal Growth ◽  
Human Glomerular Mesangial Cells

A role for G-proteins in the epidermal growth factor stimulation of phospholipase A2 in rat kidney mesangial cells

1990 ◽  
Vol 10 (4) ◽  
pp. 353-362 ◽  
Author(s):  
Nashrudeen Hack ◽  
Paula Clayman ◽  
Karl Skorecki
Keyword(s):  
Arachidonic Acid ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Phospholipase A2 ◽  
G Protein ◽  
Mesangial Cells ◽  
Rat Kidney ◽  
Glomerular Mesangial Cells ◽  
Epidermal Growth ◽  
Stimulation Of

We have previously demonstrated phospholipase C (PLC) independent activation of phospholipase A2(PLA2) by epidermal growth factor (EGF) in glomerular mesangial cells in culture. In the current study using glass beads to permeabilize [3H]- or [14C]-arachidonate labelled mesangial cells we demonstrate that guanine nucleotides modulate the EGF-mediated stimulation of arachidonic acid release (75% inhibition with 100 μM GDPβS and 108% augmentation with 100 μM GTPγS). GTPγS alone stimulated both the release of free arachidonic acid and production of diacylglycerol (DAG), while EGF itself neither stimulated DAG nor augmented the DAG response to GTPγS. These findings suggest the intermediacy of a G-protein in PLC-independent stimulation of PLA2 by a growth factor, and provide a model system for determining the relationship between G-protein intermediacy and the intrinsic tyrosine kinase activity of the growth factor receptor.

scholarly journals Epidermal growth factor and phorbol myristate acetate increase expression of the mRNA for cytosolic phospholipase A2 in glomerular mesangial cells

1993 ◽  
Vol 295 (3) ◽  
pp. 763-766 ◽  
Author(s):  
A P Maxwell ◽  
H J Goldberg ◽  
A H N Tay ◽  
Z G Li ◽  
G S Arbus ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Phospholipase A2 ◽  
Mesangial Cells ◽  
Mrna Levels ◽  
Glomerular Mesangial Cells ◽  
Pla2 Activity ◽  
Mrna Accumulation ◽  
Epidermal Growth

We have previously shown that phospholipase A2 (PLA2) activity is rapidly activated by epidermal growth factor (EGF) and phorbol 12-myristate 13-acetate (PMA) in renal mesangial cells and other cell systems in a manner that suggests a covalent modification of the PLA2 enzyme(s). This PLA2 activity is cytosolic (cPLA2) and is distinct from secretory forms of PLA2, which are also stimulated in mesangial cells in response to cytokines and other agonists. However, longer-term regulation of cPLA2 in renal cells may also occur at the level of gene expression. Cultured rat mesangial cells were used as a model system to test the effects of EGF and PMA on the regulation of cPLA2 gene expression. EGF and PMA both produced sustained increases in cPLA2 mRNA levels, with a parallel increase in enzyme activity over time. Inhibition of protein synthesis by cycloheximide increased basal cPLA2 mRNA accumulation in serum-starved mesangial cells, and the combination of EGF and cycloheximide resulted in super-induction of cPLA2 gene expression compared with EGF alone. Actinomycin D treatment entirely abrogated the effect of EGF on cPLA2 mRNA accumulation. These findings suggest that regulation of cPLA2 is achieved by factors controlling gene transcription and possibly mRNA stability, in addition to previously characterized posttranslational modifications.

scholarly journals Epidermal growth factor stimulates phospholipase A2 in vasopressin-treated rat glomerular mesangial cells

1988 ◽  
Vol 256 (2) ◽  
pp. 469-474 ◽  
Author(s):  
B L Margolis ◽  
B J Holub ◽  
D A Troyer ◽  
K L Skorecki
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Phospholipase A2 ◽  
G Proteins ◽  
Mesangial Cells ◽  
Ionophore A23187 ◽  
Glomerular Mesangial Cells ◽  
Epidermal Growth ◽  
Arachidonate Release ◽  
Phospholipase A2 Activity

Epidermal growth factor (EGF) enhances vasopressin- and ionophore-A23187-induced prostaglandin production and arachidonate release by rat glomerular mesangial cells in culture. The purpose of the present study was to delineate the phospholipid pathways involved in this effect. In cells labelled with [14C]arachidonate, EGF significantly enhanced the free arachidonate released in response to A23187 or vasopressin without enhancing the production of [14C]arachidonate-labelled diacylglycerol. EGF increased the [14C]arachidonate-labelled phosphatidic acid formed in response to vasopressin, but to a much smaller extent than it increased free arachidonate release. These results indicate that activation of phospholipase C is not sufficient to explain the increase in free arachidonate release observed on addition of EGF. To examine if EGF enhanced phospholipase A2 activity, mesangial cells were labelled with [2-2H]glycerol and [14C]-arachidonate, and the formation of arachidonate-poor lysophospholipids was studied. When combined with vasopressin, EGF significantly enhanced the formation of arachidonate-poor lysophospholipids as compared with vasopressin alone. The fate of exogenously added lysophosphatidylcholine was not altered after stimulation with vasopressin plus EGF, indicating that decreased deacylation or reacylation of the lysophospholipids was not responsible for their accumulation. Taken together, these results indicate that EGF enhances free arachidonate release by activation of phospholipase A2. The signalling mechanism responsible for the change in phospholipase A2 activity is not known, but could conceivably involve phosphorylation of modulating proteins such as lipocortin or G-proteins.

scholarly journals Epidermal Growth Factor Activates Store-Operated Calcium Channels in Human Glomerular Mesangial Cells

2001 ◽  
Vol 12 (1) ◽  
pp. 47-53
Author(s):  
RONG MA ◽  
STEVEN C. SANSOM
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Intracellular Signaling ◽  
Mesangial Cells ◽  
Cell Types ◽  
Glomerular Mesangial Cells ◽  
Signaling Mechanism ◽  
Baseline Activity ◽  
Epidermal Growth

Abstract. A cellular influx of Ca2+ is critical for initiating and maintaining growth in a variety of cell types. Experiments were performed to determine whether epidermal growth factor (EGF), which is known to initiate a proliferative response in mesangial cells, could regulate by intracellular signal transduction the store-operated Ca2+ channels (SOC) of human mesangial cells (HMC) in culture. The cell-attached patch configuration was used to monitor the activity of SOC, with 90 mM Ba2+ in the pipette and physiologic saline solution in the bath. Under control conditions, the mean NPo value was 1.06 at a holding potential of -80 mV. When 100 nM EGF was added to the bath, SOC were activated by 53%. The EGF-evoked response was dose-dependent, with a half-maximal activation concentration of 4.8 nM. An inhibitor of tyrosine kinase, i.e., tyrphostin A23 (100 μM), completely abolished EGF-evoked channel activation. EGF combined with the inactive control compound tyrphostin A1 (100 μM) elicited significant (85%) activation of SOC. Calphostin C, an inhibitor of protein kinase C (PKC), did not affect the baseline activity of SOC but abolished the EGF-evoked enhancement of SOC activity. The PKC activator phorbol-12-myristate-13-acetate (PMA) significantly activated SOC. However, the effects of PMA were duplicative rather than additive or potentiating with maximal concentrations (100 nM) of EGF, suggesting that PMA and EGF activate SOC through a common PKC pathway. In addition, downregulation of PKC via incubation of HMC with PMA for 1 to 20 h depressed both basal activity and EGF-induced activation of SOC. It is concluded that EGF stimulates SOC in HMC through an intracellular signaling mechanism involving tyrosine kinase and PKC.

scholarly journals Epidermal growth factor is synergistic with phorbol esters and vasopressin in stimulating arachidonate release and prostaglandin production in renal glomerular mesangial cells

1988 ◽  
Vol 249 (2) ◽  
pp. 587-592 ◽  
Author(s):  
B L Margolis ◽  
J V Bonventre ◽  
S G Kremer ◽  
J E Kudlow ◽  
K L Skorecki
Keyword(s):  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Epidermal Growth Factor ◽  
Mesangial Cells ◽  
Pge2 Production ◽  
Glomerular Mesangial Cells ◽  
Kinase C ◽  
Epidermal Growth ◽  
Arachidonate Release

Epidermal growth factor (EGF) is produced in large quantities by the kidney. We identified EGF-binding sites on cultured rat renal glomerular mesangial cells. These cells serve as a model system for the investigation of renal prostaglandin biosynthesis. Since EGF has been shown to modulate phospholipase activity in other cell lines, we studied the ability of EGF to increase arachidonate release and prostaglandin E2 (PGE2) production in mesangial cells. We found that EGF stimulated arachidonate release and PGE2 production in the presence of the Ca2+ ionophore A23187. This stimulation was markedly potentiated by the addition of phorbol myristate acetate (PMA), which activates protein kinase C. However, down-regulation of protein kinase C by prolonged PMA treatment did not block the ability of EGF to stimulate PGE2 production in the presence of A23187. EGF also markedly potentiated the stimulation of PGE2 production by vasopressin, which increases intracellular Ca2+ and activates protein kinase C in these cells. The stimulatory effects of EGF were not the result of prolongation or enhancement of an increase in intracellular Ca2+ produced by ionophore or vasopressin. Furthermore, the synergistic interaction of EGF with PMA and vasopressin occurred despite the fact that these agents markedly decreased EGF binding in mesangial cells, presumably owing to protein-kinase-C-mediated phosphorylation of the EGF receptor. We conclude that there exists a distinct pathway for EGF-stimulated arachidonate release and PGE2 production in rat renal glomerular mesangial cells, which is synergistic with, but not dependent on, activation of protein kinase C. In contrast with long-term mitogenic responses to EGF, this rapid response may allow delineation of the membrane phospholipid changes and signalling steps involved in this aspect of EGF action.

Effects of epidermal growth factor on collagen expression by rat kidney mesangial cells in culture

2000 ◽  
Vol 19 (1) ◽  
pp. 47-59 ◽  
Author(s):  
Michael A. Haralson ◽  
Samuel J. DiMari ◽  
Richard L. Hoover ◽  
Raymond C. Harris
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Mesangial Cells ◽  
Rat Kidney ◽  
Cells In Culture ◽  
Collagen Expression ◽  
Epidermal Growth

Mesangial cells express PDGF mRNAs and proliferate in response to PDGF

1988 ◽  
Vol 255 (4) ◽  
pp. F674-F684 ◽  
Author(s):  
P. J. Shultz ◽  
P. E. DiCorleto ◽  
B. J. Silver ◽  
H. E. Abboud
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Northern Blot Analysis ◽  
Mesangial Cells ◽  
Glomerular Mesangial Cells ◽  
Human Mesangial Cells ◽  
Human Foreskin Fibroblasts ◽  
Human Glomerular Mesangial Cells ◽  
Paracrine Growth Factor

Platelet-derived growth factor (PDGF) is a potent mitogen for cells of mesenchymal origin and is released and/or synthesized by platelets, macrophages, endothelial cells, and rat mesangial cells. In the present investigation, we found that human glomerular mesangial cells in culture release a PDGF-like protein which competes for 125I-PDGF binding to human foreskin fibroblasts and is mitogenic for these fibroblasts. The competing and to a lesser extent the mitogenic activities present in the conditioned medium are partially recognized by an anti-PDGF antibody. Northern blot analysis of poly(A)+ RNA from human mesangial cells demonstrates the expression of both PDGF A- and B-chain mRNAs. PDGF also binds to mesangial cells in a specific manner and stimulates DNA synthesis and cell proliferation. These data suggest that a PDGF-like protein secreted by mesangial cells or released from platelets, monocytes, or endothelial cells during glomerular inflammation may function as an autocrine or a paracrine growth factor for these cells. The biological role of PDGF in mediating proliferative and other inflammatory events in the glomerulus remains to be identified.

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