Exogenous ATP induces a limited cell cycle progression of arterial smooth muscle cells

Malam-Souley, R.; Campan, Michel; Gadeau, Alain‐Pierre; Des̀granges, Claude

doi:10.1152/ajpcell.1993.264.4.c783

Cited by 56 publications

(49 citation statements)

References 27 publications

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“…Moreover, extracellular ATP may be of importance in the growth regulation of mammalian cells. Stimulation of DNA synthesis has been reported for a variety of cultured cells including mouse fibroblasts, A431 epidermoid carcinoma cells and DDT,-MF-2 vas deferens cells (Huang et al, 1989), in aortic smooth muscle cells (Malam-Souley et al, 1993;Erlinge et al, 1993), endothelial cells (Van Daele et al, 1992) and mesangial cells (Schulze-Lohoff et al, 1992). It has been reported that activation of PKC and phospholipase A2 and subsequent production of prostaglandin E2 and cyclic AMP formation are obligatory early steps in a pathway resulting in ATPdependent mitogenesis Huang et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

Stimulation by extracellular ATP and UTP of the mitogen‐activated protein kinase cascade and proliferation of rat renal mesangial cells

Huwiler

Pfeilschifter

1994

British J Pharmacology

103

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1 Extracellular ATP and UTP have been reported to activate a nucleotide receptor that mediates phosphoinositide and phosphatidylcholine hydrolysis by phospholipases C and D, respectively. Here we report that ATP and UTP potently stimulate mesangial cell proliferation. 2 Both nucleotides stimulate phosphorylation and activation of mitogen-activated protein kinase and a biphasic phosphorylation of the up-stream mitogen-activated protein kinase kinase. 3 When added at 100 jiM, ATPyS, UTP and ATP were the most potent activators of mitogen-activated protein kinase. P1y-imido-ATP was somewhat less active and ADP and 2-methylthio-ATP caused a weak induction of enzyme activity. Activation of mitogen-activated protein kinase by both ATP and UTP is dose-dependently attenuated by the P2-receptor antagonist, suramin. 4 The protein kinase C activator 12-0-tetradecanoylphorbol 13-acetate, but not the biologically inactive 4a-phorbol 12,13-didecanoate, increased mitogen-activated protein kinase activity in mesangial cells, suggesting that protein kinase C may mediate nucleotide-induced stimulation of mitogen-activated protein kinase. 5 Down-regulation of protein kinase C -a and-6 isoenzymes by 4 h or 8 h treatment with phorbol ester partially inhibited ATP-and UTP-triggered mitogen-activated protein kinase activation. Moreover, a 24 h treatment of mesangial cells with phorbol ester, a regimen that also causes depletion of protein kinase C-e did not further reduce the level of mitogen-activated protein kinase stimulation. 6 The specific protein kinase C inhibitor, CGP 41251, which displayed a selectivity for the Ca2+-dependent isoenzymes, as compared to the Ca2+-independent isoenzymes did not inhibit nucleotidestimulated mitogen-activated protein kinase phosphorylation, thus implicating the involvement of a Ca2'-independent protein kinase C isoform.7 In summary, these results suggest that ATP and UTP trigger the activation of the mitogen-activated protein kinase signalling cascade in mesangial cells and this may be responsible for the potent mitogenic activity of both nucleotides.

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Section: Discussionmentioning

confidence: 99%

Stimulation by extracellular ATP and UTP of the mitogen‐activated protein kinase cascade and proliferation of rat renal mesangial cells

Huwiler

Pfeilschifter

1994

British J Pharmacology

103

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“…Cell Culture and Transfection-Rat aortic SMCs were prepared from the thoracic aortas of Wistar rats and cultured as described previously (26). SMCs from passages 10 to 20 were used.…”

Section: Methodsmentioning

confidence: 99%

UTP Induces Osteopontin Expression through a Coordinate Action of NFκB, Activator Protein-1, and Upstream Stimulatory Factor in Arterial Smooth Muscle Cells

Renault

Jalvy

Potier

et al. 2005

Journal of Biological Chemistry

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Osteopontin (OPN) is an important chemokinetic agent for several cell types. Our earlier studies have shown that its expression is essential for uridine triphosphate (UTP)-mediated migration of vascular smooth muscle cells. We demonstrated previously that the activation of an AP-1 binding site located 76 bp upstream of the transcription start in the rat OPN promoter is involved in the induction of OPN expression. In this work, using a luciferase promoter deletion assay, we identified a new region of the rat OPN promoter (؊1837 to ؊1757) that is responsive to UTP. This region contains an NFB site located at ؊1800 and an Ebox located at ؊1768. Supershift electrophoretic mobility shift assay and chromatin immunoprecipitation assays identified NFB and USF-1/USF-2 as the DNA binding proteins induced by UTP, respectively, for these two sites. Using dominant negative mutants of IB kinase and USF transcription factors, we confirmed that NFB and USF-1/USF-2 are involved in the UTP-mediated expression of OPN. Using a pharmacological approach, we demonstrated that USF proteins are regulated by the extracellular signal-regulated kinase (ERK)1/2 pathway, just as the earlier discovered AP-1 complex, whereas NFB is up-regulated through PKC␦ signals. Finally, our work suggests that the UTPstimulated OPN expression involves a coordinate regulation of PKC␦-NFB, ERK1/2-USF, and ERK1/2/ NAD(P)H oxidase AP-1 signaling pathways. Osteopontin (OPN)1 is a multifunctional phosphoprotein secreted by many cell types such as osteoclasts, lymphocytes, macrophages, epithelial cells, and smooth muscle cells (SMCs).Its expression is induced during vessel remodeling, as well as wound healing and bone synthesis (1). Overexpression of OPN can be found in pathological settings, such as immunological disorders, neoplastic transformation, metastasis, and formation of urinary stones. Its role in cell migration has been established in vitro in various cell types, including osteoclasts (2), macrophages (3), endothelial cells (4), and SMCs (5, 6). In vivo studies have established that OPN contributes to SMC recruitment into atherosclerotic plaques (7) and neointimal thickening (8), to osteoclast recruitment during bone resorption, (2) and to macrophage recruitment at inflammatory sites (atherosclerotic plaque, granulomas) (3).In the context of vascular remodeling, soluble factors, such as angiotensin II, basic fibroblast growth factor, plateletderived growth factor, interleukin-1 (9), and the nucleotides ATP and UTP (10), all induce expression of OPN. Moreover, nucleotides also modulate contraction, proliferation, and migration of vascular SMCs (11). They act through G proteincoupled P2Y receptors (12) and activate phospholipase C, resulting in elevated levels of intracellular free Ca 2ϩ and activation of PKC. In addition, they induce ROS production through NAD(P)H oxidase (13). Several transcription factors, such as NFAT, AP-1, cAMP-responsive element-binding protein, serum-responsive factor, STAT, and NFB are induced in UTP-stimulated SMCs (14), contro...

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“…In vitro studies of VSMC have shown that extracellular nucleotides induce cell cycle progression and proliferation [6][7][8]. For example, UTP has chemotactic effects on VSMC migration which involve Rho and mitogen-activated purine signaling via P2Y receptor subtypes [3,[9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Vascular smooth muscle cell expression of ectonucleotidase CD39 (ENTPD1) is required for neointimal formation in mice

Behdad

Sun

Khalpey

et al. 2009

Purinergic Signalling

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Vascular smooth muscle cell (VSMC) migration and proliferation are critical steps in the pathogenesis of atherosclerosis, post-angioplasty restenosis, neointimal hyperplasia, and chronic allograft rejection. Extracellular nucleotides are known to influence both migration and proliferation of VSMC. Although it is well established that vascular endothelial Cd39/ENTPD1 regulates blood nucleotide concentrations, whether Cd39 associated with VSMC also impacts vascular wall pathology in mice has not been investigated. The objective of this paper is to determine levels of expression of Cd39 on VSMC and functional consequences of gene deletion in vitro and in vivo. Cd39 is the major ectonucleotidase in VSMC, as shown by substantive decreases in ecto-ATPase and -ADPase activity in Cd39-null cells compared to wild type. Significant decreases in neointimal lesion formation are observed in Cd39-null mice at 21 days post arterial balloon injury. Stimulated Cd39-null VSMC have pronounced proliferative responses in vitro. However, using Transwell systems, we show that Cd39-null VSMC fail to migrate in response to ATP, UTP, and PDGF. Cd39 is the dominant ectonucleotidase expressed by VSMC. Deletion of Cd39 in mice results in decreased neointimal formation after vascular injury and is associated with impaired VSMC migration responses in vitro.

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Exogenous ATP induces a limited cell cycle progression of arterial smooth muscle cells

Cited by 56 publications

References 27 publications

Stimulation by extracellular ATP and UTP of the mitogen‐activated protein kinase cascade and proliferation of rat renal mesangial cells

Stimulation by extracellular ATP and UTP of the mitogen‐activated protein kinase cascade and proliferation of rat renal mesangial cells

UTP Induces Osteopontin Expression through a Coordinate Action of NFκB, Activator Protein-1, and Upstream Stimulatory Factor in Arterial Smooth Muscle Cells

Vascular smooth muscle cell expression of ectonucleotidase CD39 (ENTPD1) is required for neointimal formation in mice

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