scholarly journals Role of c-Abl tyrosine kinase in smooth muscle cell migration

2014 ◽  
Vol 306 (8) ◽  
pp. C753-C761 ◽  
Author(s):  
Rachel A. Cleary ◽  
Ruping Wang ◽  
Omar Waqar ◽  
Harold A. Singer ◽  
Dale D. Tang
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Cell Adhesion ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Leading Edge ◽  
Actin Dynamics ◽  
Cell Edge ◽  
Smooth Muscle Cell Migration

c-Abl is a nonreceptor protein tyrosine kinase that has a role in regulating smooth muscle cell proliferation and contraction. The role of c-Abl in smooth muscle cell migration has not been investigated. In the present study, c-Abl was found in the leading edge of smooth muscle cells. Knockdown of c-Abl by RNA interference attenuated smooth muscle cell motility as evidenced by time-lapse microscopy. Furthermore, the actin-associated proteins cortactin and profilin-1 (Pfn-1) have been implicated in cell migration. In this study, cell adhesion induced cortactin phosphorylation at Tyr-421, an indication of cortactin activation. Phospho-cortactin and Pfn-1 were also found in the cell edge. Pfn-1 directly interacted with cortactin in vitro. Silencing of c-Abl attenuated adhesion-induced cortactin phosphorylation and Pfn-1 localization in the cell edge. To assess the role of cortactin/Pfn-1 coupling, we developed a cell-permeable peptide. Treatment with the peptide inhibited the interaction of cortactin with Pfn-1 without affecting cortactin phosphorylation. Moreover, treatment with the peptide impaired the recruitment of Pfn-1 to the leading edge and cell migration. Finally, β1-integrin was required for the recruitment of c-Abl to the cell edge. Inhibition of actin dynamics impaired the spatial distribution of c-Abl. These results suggest that β1-integrin may recruit c-Abl to the leading cell edge, which may regulate cortactin phosphorylation in response to cell adhesion. Phosphorylated cortactin may facilitate the recruitment of Pfn-1 to the cell edge, which promotes localized actin polymerization, leading edge formation, and cell movement. Conversely, actin dynamics may strengthen the recruitment of c-Abl to the leading edge.

scholarly journals Unexpected Role of the Copper Transporter ATP7A in PDGF-Induced Vascular Smooth Muscle Cell Migration

2010 ◽  
Vol 107 (6) ◽  
pp. 787-799 ◽  
Author(s):  
Takashi Ashino ◽  
Varadarajan Sudhahar ◽  
Norifumi Urao ◽  
Jin Oshikawa ◽  
Gin-Fu Chen ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Copper Transporter ◽  
Smooth Muscle Cell Migration

scholarly journals The role of integrins in saphenous vein vascular smooth muscle cell migration

1997 ◽  
Vol 25 (6) ◽  
pp. 1061-1069 ◽  
Author(s):  
Hiroyuki Itoh ◽  
Peter R. Nelson ◽  
Leila Mureebe ◽  
Arie Horowitz ◽  
K.Craig Kent
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Saphenous Vein ◽  
Smooth Muscle Cell Migration

scholarly journals Epac1 is upregulated during neointima formation and promotes vascular smooth muscle cell migration

2008 ◽  
Vol 295 (4) ◽  
pp. H1547-H1555 ◽  
Author(s):  
Utako Yokoyama ◽  
Susumu Minamisawa ◽  
Hong Quan ◽  
Toru Akaike ◽  
Meihua Jin ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Remodeling ◽  
Muscle Cells ◽  
Smooth Muscle Cell Migration

Vascular remodeling after mechanoinjury largely depends on the migration of smooth muscle cells, an initial key step to wound healing. However, the role of the second messenger system, in particular, the cAMP signal, in regulating such remodeling remains controversial. Exchange protein activated by cAMP (Epac) has been identified as a new target molecule of the cAMP signal, which is independent from PKA. We thus examined whether Epac plays a distinct role from PKA in vascular remodeling. To examine the role of Epac and PKA in migration, we used primary culture smooth muscle cells from both the fetal and adult rat aorta. A cAMP analog selective to PKA, 8-(4-parachlorophenylthio)-cAMP (pCPT-cAMP), decreased cell migration, whereas an Epac-selective analog, 8-pCPT-2′- O-Me-cAMP, enhanced migration. Adenovirus-mediated gene transfer of PKA decreased cell migration, whereas that of Epac1 significantly enhanced cell migration. Striking morphological differences were observed between pCPT-cAMP- and 8-pCPT-2′- O-Me-cAMP-treated aortic smooth muscle cells. Furthermore, overexpression of Epac1 enhanced the development of neointimal formation in fetal rat aortic tissues in organ culture. When the mouse femoral artery was injured mechanically in vivo, we found that the expression of Epac1 was upregulated in vascular smooth muscle cells, whereas that of PKA was downregulated with the progress of neointimal thickening. Our findings suggest that Epac1, in opposition to PKA, increases vascular smooth muscle cell migration. Epac may thus play an important role in advancing vascular remodeling and restenosis upon vascular injury.

Effect of Pulse Pressure on Vascular Smooth Muscle Cell Migration: The Role of Urokinase and Matrix Metalloproteinase

1999 ◽  
Vol 81 (02) ◽  
pp. 293-300 ◽  
Author(s):  
Paul Cahill ◽  
Mindy Hirsch ◽  
Yi-Ning Wang ◽  
James Sitzmann ◽  
Steve Okada ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Matrix Metalloproteinase ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Pulse Pressure ◽  
Pulsatile Flow ◽  
Umbilical Vein ◽  
Smooth Muscle Cell Migration

SummaryPlasminogen activator (PA) expression plays an important role in smooth muscle cell (SMC) migration and may therefore contribute to mechanical force-induced arterialization of vein grafts. The aim of this study was to determine whether pulse pressure due to pulsatile flow modulates SMC migration via urokinase (u-PA)-dependent mechanisms. Using a perfused transcapillary culture system, human umbilical vein SMC were exposed to pulse pressures (0-56 mmHg), in the absence or presence of human umbilical vein endothelial cells (EC) by varying pulsatile flow rates (0 ml/min to 25 ml/min). SMC cultured in the absence of EC increased their migration following exposure to increased pulse pressure (248 ± 14%). Both u-PA and matrix metalloproteinase 1 (MMP-1) expression was significantly elevated in SMC exposed to pressure as compared to static controls. The role of proteases in the pulse pressure-induced enhancement of SMC migration was confirmed following pretreatment with aprotinin, an anti u-PA antibody and metalloproteinase inhibitors (181 ± 14% for aprotinin vs. 256 ± 25% for control, 108 ± 4% for anti-u-PA antibody vs. 233 ± 17% for non-immune IgG, and 114 ± 9% for BB-94, 105 ± 7% for BB-3103 vs. 222 ± 5% for control). Using SMC derived from u-PA gene knockout mice, the SMC migratory response to increased pulse pressure was completely inhibited despite a significant increase in MMP expression in these cells. These results suggest that pulse pressure due to pulsatile flow induces SMC migration in vitro via u-PA and MMP-dependent mechanisms. Moreover, u-PA gene deletion results in blunting of pressure-induced SMC migration despite the endogenous upregulation of metalloproteinase. Modulation of u-PA expression by pressure may thus represent an important mechanism whereby hemodynamic forces regulate smooth muscle cell migration.

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