Hepatocyte growth factor modulates migration and proliferation of human microvascular endothelial cells in culture

Morimoto, Akio; Okamura, Kazuki; Hamanaka, Ryoji; Sato, Yasufumi; Shima, Nobuyuki; Higashio, Kanji; Kuwano, Michihiko

doi:10.1016/0006-291x(91)91924-2

Cited by 127 publications

(56 citation statements)

References 19 publications

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“…It is unclear if these cells were recruited from the blood, or if the HGF induced replication of resident cells. Replication of NP cells in response to HGF may reflect the fact that blood monocytes 48 and endothelial cells 49 can replicate in response to HGF.…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide potentiates the effect of hepatocyte growth factor on hepatocyte replication in rats by augmenting AP-1 activity

et al. 1999

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The liver regenerates by replication of differentiated hepatocytes after damage or removal of part of the liver. Although several growth factors and signaling pathways are activated during regeneration, it is unclear as to which of these are essential for hepatocyte replication. We show here that low-(1 mg/kg) and high-(10 mg/kg) dose hepatocyte growth factor (HGF) induced replication of 2.1% and 11.1% of hepatocytes in rats, respectively. Lipopolysaccharide The normal liver has a remarkable ability to replicate in response to injury or partial hepatectomy (PH). A better understanding of the molecular mechanisms responsible for this process might enable liver regeneration to be induced in liver insufficiency states such as cirrhosis. In addition, this information might facilitate gene therapy, as some vectors only transduce dividing cells, and hepatocytes are normally quiescent. 1

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Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide potentiates the effect of hepatocyte growth factor on hepatocyte replication in rats by augmenting AP-1 activity

et al. 1999

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“…Others have investigated motility (38) and chemotaxis ( 19) of individual cells. Previous attempts to model sheet migration have generally involved the radial migration ofcells from tissue explants (39)(40)(41) or the creation ofwounds in cell monolayers (42,43) or intact tissues (8,(13)(14)(15)(16)(17)43). Studies ofintact tissue or tissue explants may be difficult to control while cell injury occurring in wounding may release intracellular bioactive agents which confuse the assay (42).…”

Section: Discussionmentioning

confidence: 99%

Human enterocyte (Caco-2) migration is modulated in vitro by extracellular matrix composition and epidermal growth factor.

Basson¹,

Modlin²,

Madri³

1992

J. Clin. Invest.

181

131

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The modulation of enterocyte sheet migration was studied using Caco-2 cells, a well-differentiated human colonic cell line. Although Caco-2 cells attached and spread equivalently over collagen types I, III, IV, and V and laminin, migration over laminin was significantly slower than migration over the collagen types. Fibronectin was a poor substrate for attachment, spreading, and migration. Epidermal growth factor (EGF) stimulated migration over laminin but did not alter Caco-2 migration over collagen or fibronectin. This effect was independent of cell proliferation, which was stimulated equivalently on both laminin and collagen I. Expression and organization of cell surface receptors for matrix (integrins) were studied using antibodies specific for f and a integrin subunits. Integrin surface expression was assessed by immunoprecipitation of surface l25i dinated control and EGF-treated cells. fi1 surface pools did not change substantially in any condition studied. al subunit pools were decreased after EGF treatment on collagen I but al pools increased after EGF treatment on laminin. Surface pools of a2 subunits were increased following EGF treatment whether cells were cultured on laminin or collagen I. However, traditional immunofluorescent and laser confocal imaging demonstrated substantial differences in the character of a2 subunit organization between collagen and laminin in the migrating cell front. Furthermore, a functional antibody to the a2 subunit inhibited EGF stimulation of migration over laminin without substantial effects on basal migration over laminin or collagen I. Thus, EGF appears to exert a matrix-specific effect on enterocyte migration by modulation of integrin expression and organization. (J. Clin. Invest. 1992. 90:15-23.)

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“…When hepatocyte growth factor (HGF or scatter factor), a powerful stimulus for migration and angiogenesis (32,33), was utilized as the agonist, PKC␣ EC traversed the membrane at a significantly greater rate than did PKC␦ or control EC (Fig. 3), suggesting a migratory response mediated by PKC␣ to this stimulus.…”

Section: Isolation and Characterization Of Overexpressing Cellmentioning

confidence: 99%

Enhancement of Migration by Protein Kinase Cα and Inhibition of Proliferation and Cell Cycle Progression by Protein Kinase Cδ in Capillary Endothelial Cells

Harrington

Löffler

Nelson

et al. 1997

Journal of Biological Chemistry

122

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Activation of protein kinase C (PKC) induces angiogenesis, migration, and proliferation of endothelial cells (EC), but can also prevent growth factor-induced EC proliferation. To determine whether these disparate effects are mediated by substrates of individual PKC isoenzymes, PKC␣ and PKC␦ were overexpressed in rat microvascular EC. Basal and stimulated migration were enhanced in PKC␣ EC compared with either PKC␦ or control EC. Serum-induced growth of PKC␦ EC was decreased, while that of PKC␣ cells was similar to control EC. Phorbol ester markedly inhibited PKC␦ EC growth but enhanced growth of PKC␣ and control EC. To determine possible causes for this altered proliferation, the effect of PKC␦ on adhesion, mitogen-activated protein kinase activity, and cell cycle progression was measured. Adherence of PKC␦ EC to vitronectin was significantly enhanced. Serum-induced extracellular signalregulated kinase-2 activity was increased equally in both PKC␣ and PKC␦ EC above that of control, while extracellular signal-regulated kinase-1 activity was similar in all EC. Cell cycle analysis suggested that PKC␦ EC entered S phase inappropriately and were delayed in passage through S phase. Thus, PKC␣ may mediate some proangiogenic effects of PKC activation; conversely, PKC␦ may direct antiangiogenic aspects of overall PKC activation, including slowing of the cell cycle progression.The formation of new blood vessels and the repair of those damaged by disease or injury depend upon endothelial migration and proliferation (1, 2). Several external agents that promote or inhibit proliferation and migration have been identified (3, 4), but the intracellular messengers that mediate these processes are less clear.Activation of the serine-threonine kinase protein kinase C (PKC) 1 by phorbol esters induces migration, proliferation (5), and tube formation of cultured endothelial cells (6, 7) and causes angiogenesis in vivo (7-9). In addition, chemical inhibitors of PKC or the down-regulation of PKC by prolonged treatment with phorbol esters abrogates the proliferative effects induced by growth factors and mitogens (10, 11) and also enhances endothelial permeability (12, 13) and alters the expression level of several fibrinolytic enzymes and their inhibitors (14). In contrast, treatment of endothelial cells with direct activators of PKC alters some responses that are usually associated with stimulation by physiologic agonists (15) and, under some conditions, can prevent growth factor-induced proliferation (16). This apparent paradox might be explained by the fact that the PKC family is composed of related but structurally distinct isoenzymes, each a product of separate genes and with discrete cofactor requirements, substrate specificity, and tissue distribution (16 -18). Since phorbol esters activate multiple isoenzymes of PKC, the possibility is raised that each PKC isoenzyme may selectively mediate separate, and perhaps opposing, effects within stimulated endothelial cells.Preliminary studies in our laboratory revealed that rat capillar...

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Hepatocyte growth factor modulates migration and proliferation of human microvascular endothelial cells in culture

Cited by 127 publications

References 19 publications

Lipopolysaccharide potentiates the effect of hepatocyte growth factor on hepatocyte replication in rats by augmenting AP-1 activity

Lipopolysaccharide potentiates the effect of hepatocyte growth factor on hepatocyte replication in rats by augmenting AP-1 activity

Human enterocyte (Caco-2) migration is modulated in vitro by extracellular matrix composition and epidermal growth factor.

Enhancement of Migration by Protein Kinase Cα and Inhibition of Proliferation and Cell Cycle Progression by Protein Kinase Cδ in Capillary Endothelial Cells

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