Extracellular matrix proteins are potent agonists of human smooth muscle cell migration

Nelson, Peter R.; Yamamura, Shinji; Kent, K. Craig

doi:10.1016/s0741-5214(96)70141-6

Cited by 60 publications

(60 citation statements)

References 15 publications

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“…33 During atherogenesis or following vascular injury, osteopontin expression increases and is thought to enhance VSM migration via ␣ v ␤ 3 integrin signaling. 34 -36 Similar promigratory effects have been reported for each of the major constituents of the extracellular matrix of the vessel wall, including collagens I and IV and laminin 37 (see Table 1). Integrin ligation is necessary for VSM adhesion to the matrix, and it triggers promigratory intracellular signaling cascades from the "outside in."…”

Section: Mechanisms Of Cell Migration Proximal Signals and Initial Trsupporting

confidence: 57%

“…Transforming growth factor-␤ 1 (TGF␤ 1 ) 183,184 Tumor necrosis factor-␣ (TNF␣) 185,161 Thrombin 186 Urokinase plasminogen activator 187,188 Vascular endothelial growth factor (VEGF) 189,190 Extracellular matrix components Collagen I, IV 37 Collagen VIII 191,192 Sphingosine-1 phosphate (S1P) 75,76 formins (mDia1 and mDia2), which act on the plus end in concert with profilin. The formin mDia1 is activated by RhoA, and mDia2 is activated by Cdc42.…”

Section: Pdgf 23mentioning

confidence: 99%

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Mechanisms of Vascular Smooth Muscle Cell Migration

Gerthoffer

2007

Circulation Research

407

350

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Abstract-Smooth muscle cell migration occurs during vascular development, in response to vascular injury, and during atherogenesis. Many proximal signals and signal transduction pathways activated during migration have been identified, as well as components of the cellular machinery that affect cell movement. In this review, a summary of promigratory and antimigratory molecules belonging to diverse chemical and functional families is presented, along with a summary of key signaling events mediating migration. Extracellular molecules that modulate migration include small biogenic amines, peptide growth factors, cytokines, extracellular matrix components, and drugs used in cardiovascular medicine. Promigratory stimuli activate signal transduction cascades that trigger remodeling of the cytoskeleton, change the adhesiveness of the cell to the matrix, and activate motor proteins. This review focuses on the signaling pathways and effector proteins regulated by promigratory and antimigratory molecules. Prominent pathways include phosphatidylinositol 3-kinases, calcium-dependent protein kinases, Rho-activated protein kinase, p21-activated protein kinases, LIM kinase, and mitogen-activated protein kinases. Important downstream targets include myosin II motors, actin capping and severing proteins, formins, profilin, cofilin, and the actin-related protein-2/3 complex. Actin filament remodeling, focal contact remodeling, and molecular motors are coordinated to cause cells to migrate along gradients of chemical cues, matrix adhesiveness, or matrix stiffness. The result is recruitment of cells to areas where the vessel wall is being remodeled. Vessel wall remodeling can be antagonized by common cardiovascular drugs that act in part by inhibiting vascular smooth muscle cell migration. Several therapeutically important drugs act by inhibiting cell cycle progression, which may reduce the population of migrating cells. (Circ Res. 2007;100:607-621.)

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Section: Mechanisms Of Cell Migration Proximal Signals and Initial Trsupporting

confidence: 57%

Section: Pdgf 23mentioning

confidence: 99%

Mechanisms of Vascular Smooth Muscle Cell Migration

Gerthoffer

2007

Circulation Research

407

350

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“…An elevated level of FN is found in hyperplastic plaques, and we and others (26,40) have demonstrated that FN is a potent agonist of SMC migration. E47 cells, a human arterial SMC line derived from a carotid plaque, were made quiescent by incubation in 0.5% serum for 48 h. Chemotaxis of E47 cells toward soluble FN was determined using a transwell assay.…”

Section: Rapamycin Inhibits Fn-induced Smc Migrationmentioning

confidence: 55%

“…Levels of fibronectin (FN) are increased; FN, in turn, is a potent activator of SMCs (28). We and others (26,40) have previously demonstrated that ECM proteins, including FN, are potent stimulants of vascular SMC chemotaxis. The effect of these matrix proteins can be at least equivalent to that of the prototypical chemokine PDGF-BB (26).…”

mentioning

confidence: 87%

“…We and others (26,40) have previously demonstrated that ECM proteins, including FN, are potent stimulants of vascular SMC chemotaxis. The effect of these matrix proteins can be at least equivalent to that of the prototypical chemokine PDGF-BB (26). Stimulation of cellular migration by ECM proteins is mediated by a diverse class of heterodimeric ␣␤-membrane receptors known as integrins (7,11,12).…”

mentioning

confidence: 87%

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Rapamycin inhibits fibronectin-induced migration of the human arterial smooth muscle line (E47) through the mammalian target of rapamycin

Sakakibara¹,

Liu²,

Hollenbeck³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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has not yet been defined. In these studies, we found that rapamycin (10 nM) markedly diminished chemotaxis of E47 cells (a cell line derived from human atherosclerotic plaques) and rat aortic SMCs toward FN as well as type I collagen and laminin; however, a period of preincubation Ͼ20 h was required. Subsequently, we showed that treatment with FN induced a rapid activation of mTOR as well as its downstream effector, S6 kinase (S6K). Moreover, FN-induced activation of both proteins was inhibited by preincubation with rapamycin for only 30 min. We then explored the upstream signaling pathway through which FN might mediate mTOR activation. A blocking antibody to ␣v␤3 inhibited FN-induced mTOR/ S6K activation as well as E47 cell chemotaxis, implicating ␣v␤3 as the integrin receptor responsible for initiating FN-induced migration. Moreover, preincubation of E47 cells with wortmannin or LY-294002 blocked FN-induced mTOR/S6K activation, demonstrating that phosphatidylinositol 3-kinase (PI3K) plays a critical role in this rapamycin-sensitive signaling pathway. It has been previously suggested that rapamycin's effect on migration maybe related to enhancement of p27 kip1 . However, treatment of E47 cells with rapamycin did not alter the level of p27 kip1 in the presence or absence of FN. Taken together, our data demonstrate that rapamycin inhibits FN-induced SMC migration through a pathway that involves at least ␣v␤3-integrin, PI3K, mTOR, and S6K. S6 kinase; phosphatidylinositol 3-kinase; integrin; p27 kip1 ; extracellular matrix proteins RAPAMYCIN (sirolimus), initially developed as antibiotic and then as an immunosuppressant, has recently been used in drug-eluting stents to prevent restenosis. In several clinical trials, these stents have reduced the rate of significant restenosis from ϳ30 to Ͻ5% (25,33,35). The mechanism that underlies rapamycin's potent effect on intimal hyperplasia is not yet completely understood; however, it is believed rapamycin's action may be in part mediated through a direct effect on vascular smooth muscle cells (SMCs) (20).The inhibitory effect of rapamycin on vascular SMC proliferation has been well established. Both in vitro and in vivo, rapamycin inhibits cell cycle progression of vascular SMCs from G 1 to S (6, 13, 22); this effect may be related to an induction of p27 kip1 , a cyclin-dependent kinase (CDK) inhibitor (20). Rapamycin has also been found to inhibit migration of cultured SMCs. Treatment of vascular SMCs with rapamycin diminishes the ability of SMCs to migrate toward the potent chemokine platelet-derived growth factor (PDGF) (29).Rapamycin's cellular effects appear to be mediated through the intracellular protein target of rapamycin (TOR). TORs were first identified in Saccharomyces cerevisiae during a genetic screening for mutants resistant to growth inhibition by rapamycin (10). TOR and its mammalian homolog (mTOR) are members of a unique family of protein kinases that contain domains similar to lipid kinases such as phosphatidylinositol 3-kinase (PI3K) (14). Several key pr...

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Smooth Muscle Cell Hypertrophy, Proliferation, Migration and Apoptosis in Pulmonary Hypertension

Tajsic

Morrell

2010

Comprehensive Physiology

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Pulmonary hypertension is a multifactorial disease characterized by sustained elevation of pulmonary vascular resistance (PVR) and pulmonary arterial pressure (PAP). Central to the pathobiology of this disease is the process of vascular remodelling. This process involves structural and functional changes to the normal architecture of the walls of pulmonary arteries (PAs) that lead to increased muscularization of the muscular PAs, muscularization of the peripheral, previously nonmuscular, arteries of the respiratory acinus, formation of neointima, and formation of plexiform lesions. Underlying or contributing to the development of these lesions is hypertrophy, proliferation, migration, and resistance to apoptosis of medial cells and this article is concerned with the cellular and molecular mechanisms of these processes. In the first part of the article we focus on the concept of smooth muscle cell phenotype and the difficulties surrounding the identification and characterization of the cell/cells involved in the remodelling of the vessel media and we review the general mechanisms of cell hypertrophy, proliferation, migration and apoptosis. Then, in the larger part of the article, we review the factors identified thus far to be involved in PH intiation and/or progression and review and discuss their effects on pulmonary artery smooth muscle cells (PASMCs) the predominant cells in the tunica media of PAs.

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Extracellular matrix proteins are potent agonists of human smooth muscle cell migration

Cited by 60 publications

References 15 publications

Mechanisms of Vascular Smooth Muscle Cell Migration

Mechanisms of Vascular Smooth Muscle Cell Migration

Rapamycin inhibits fibronectin-induced migration of the human arterial smooth muscle line (E47) through the mammalian target of rapamycin

Smooth Muscle Cell Hypertrophy, Proliferation, Migration and Apoptosis in Pulmonary Hypertension

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