Escin attenuates cell migration induced with extracellular nucleotides by reducing sPLA2 activity

2012 ◽  
Vol 56 (5-6) ◽  
pp. 378
Author(s):  
Oliwia Zegrocka-Stendel ◽  
Joanna Drozdowska ◽  
Malgorzata Dutkiewicz ◽  
Dorota Maciejko ◽  
Anna Paradowska ◽  
...  
Keyword(s):  
Cell Migration ◽  
Extracellular Nucleotides ◽  
Spla2 Activity

Abstract 340: Recombinant Soluble Apyrase Inhibits Vascular Smooth Muscle Cell Migration

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Oluwaseun Adeola ◽  
Yan Ji ◽  
Phillip Fish ◽  
Tammy Strawn ◽  
Gary A Weisman ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Purinergic Receptor ◽  
Neointimal Hyperplasia ◽  
Receptor Activation ◽  
Vehicle Control ◽  
Extracellular Nucleotides ◽  
Lower Chamber ◽  
Upper Chamber

Background: Purinergic receptor activation by extracellular nucleotides is involved in thrombosis and neointimal hyperplasia that accompany atherosclerosis and postangioplasty restenosis. Human apyrases [ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDases)] are membrane bound enzymes that hydrolyze extracellular nucleotides, thereby inhibiting purinergic receptor activation. CD39, the first identified human apyrase, is constitutively expressed on endothelial cell (EC) and vascular smooth muscle cell (VSMC) surfaces. APT102, a recombinant soluble form of CD39L3, has been shown to reduce platelet activation through its ADPase activity, but its effects on VSMC and EC function are yet to be established. We tested the hypothesis that APT102 will inhibit migration of VSMCs and ECs. Methods: We studied cell migration using a modified Boyden chamber assay in which 5x10 4 cells suspended in 0.2% FBS/DMEMF12 were added to the upper chamber of transwells separated from the lower chamber medium by a microporous membrane through which VSMCs and ECs can migrate. APT102 (100 nM) or vehicle control was added to the upper chamber; lower chamber contained 2.5% FBS/DMEMF12 and either ATP (10 μM) or vehicle control. Transwells were incubated at 37 0 C for 6 h, after which cells that migrated through pores and adhered to the lower chamber side of the membrane were fixed, stained and counted. Results: ATP (10μM) significantly enhanced migration of both VSMCs and ECs. APT102 significantly inhibited VSMC migration and completely abrogated the pro-migratory effect of ATP. In contrast, APT102 had no inhibitory effect on EC migration, either spontaneous or ATP-enhanced. Conclusion: APT102 inhibits VSMC but not EC migration. These results suggest that pharmacological targeting of extracellular nucleotides may provide a safe and effective therapeutic strategy to inhibit neointimal hyperplasia and restenosis after angioplasty, without delaying endothelial cell recovery, which is a significant limitation of drug-eluting stents. Further studies are needed to clarify the mechanism(s) underlying the differential effect of extracellular nucleotide degradation by APT102 on VSMC and EC migration.

scholarly journals Modulation of endothelial cell migration by extracellular nucleotides

2005 ◽  
Vol 93 (04) ◽  
pp. 735-742 ◽  
Author(s):  
Laurie Erb ◽  
Katarzyna Koziak ◽  
Robert Jarzyna ◽  
Marcia Wink ◽  
Olaf Guckelberger ◽  
...  
Keyword(s):  
Cell Migration ◽  
Endothelial Cell ◽  
P2 Receptors ◽  
Cellular Adhesion ◽  
Extracellular Nucleotides ◽  
Endothelial Cell Migration ◽  
Free Calcium ◽  
Receptor Subtypes ◽  
Dependent Manner ◽  
Cell Functions

SummaryExtracellular nucleotides bind to type-2 purinergic/pyrimidinergic (P2) receptors that mediate various responses, such as cell activation, proliferation and apoptosis, implicated in inflammatory processes. The role of P2 receptors and their associated signal transduction pathways in endothelial cell responses has not been fully investigated. Here, it is shown that stimulation of human umbilical vein endothelial cells (HUVEC) with extracellular ATP or UTP increased intracellular free calcium ion concentrations ([Ca2+]i), induced phosphorylation of focal adhesion kinase (FAK), p130cas and paxillin, and caused cytoskeletal rearrangements with consequent cell migration. Furthermore, UTP increased migration of HUVEC in a phosphatidylinositol 3-kinase (PI3-K)-dependent manner. BAPTA or thapsigargin inhibited the extracellular nucleotide-induced increase in [Ca2+]i, a response crucial for both FAK phosphorylation and cell migration. Furthermore, long-term exposure of HUVEC to ATP and UTP, agonists of the G protein-coupled P2Y2 and P2Y4 receptor subtypes, caused upregulation of αv integrin expression, a cell adhesion molecule known to directly interact with P2Y2 receptors. Our results suggest that extracellular nucleotides modulate signaling pathways in HUVEC influencing cell functions, such as cytoskeletal changes, cellular adhesion and motility, typically associated with integrin-activation and the action of growth factors. We propose that P2Y2 and possibly P2Y4 receptors mediate those responses that are important in vascular inflammation, atherosclerosis and angiogenesis.

scholarly journals Extracellular Nucleotides Induce Arterial Smooth Muscle Cell Migration Via Osteopontin

2001 ◽  
Vol 89 (9) ◽  
pp. 772-778 ◽  
Author(s):  
Hervé Chaulet ◽  
Claude Desgranges ◽  
Marie-Ange Renault ◽  
Françoise Dupuch ◽  
Gérome Ezan ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Extracellular Nucleotides ◽  
Arterial Smooth Muscle Cell ◽  
Arterial Smooth Muscle ◽  
Smooth Muscle Cell Migration

Neutrophil migration through in vitro interstitial matrix

1992 ◽  
Vol 50 (1) ◽  
pp. 894-895
Author(s):  
J. Roemer ◽  
S.R. Simon
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Cell Migration ◽  
Smooth Muscle Cells ◽  
Inflammatory Cell ◽  
Neutrophil Migration ◽  
Culture Conditions ◽  
Aortic Smooth Muscle ◽  
Specific Culture

We are developing an in vitro interstitial extracellular matrix (ECM) system for study of inflammatory cell migration. Falcon brand Cyclopore membrane inserts of various pore sizes are used as a support substrate for production of ECM by R22 rat aortic smooth muscle cells. Under specific culture conditions these cells produce a highly insoluble matrix consisting of typical interstitial ECM components, i.e.: types I and III collagen, elastin, proteoglycans and fibronectin.

The role of DUBs in the post-translational control of cell migration

2019 ◽  
Vol 63 (5) ◽  
pp. 579-594 ◽  
Author(s):  
Guillem Lambies ◽  
Antonio García de Herreros ◽  
Víctor M. Díaz
Keyword(s):  
Cell Migration ◽  
Translational Control ◽  
Epithelial To Mesenchymal Transition ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Mesenchymal Transition ◽  
Tgfβ Receptors ◽  
Fundamental Process ◽  
Multistep Process

Abstract Cell migration is a multifactorial/multistep process that requires the concerted action of growth and transcriptional factors, motor proteins, extracellular matrix remodeling and proteases. In this review, we focus on the role of transcription factors modulating Epithelial-to-Mesenchymal Transition (EMT-TFs), a fundamental process supporting both physiological and pathological cell migration. These EMT-TFs (Snail1/2, Twist1/2 and Zeb1/2) are labile proteins which should be stabilized to initiate EMT and provide full migratory and invasive properties. We present here a family of enzymes, the deubiquitinases (DUBs) which have a crucial role in counteracting polyubiquitination and proteasomal degradation of EMT-TFs after their induction by TGFβ, inflammatory cytokines and hypoxia. We also describe the DUBs promoting the stabilization of Smads, TGFβ receptors and other key proteins involved in transduction pathways controlling EMT.

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