Modulation of transforming growth factor beta receptor levels on microvascular endothelial cells during in vitro angiogenesis.

Sankar, Sabita; Mahooti-Brooks, Negar; Bensen, L; McCarthy, Thomas L.; Centrella, Michael; Madri, Joseph A.

doi:10.1172/jci118565

Cited by 148 publications

(88 citation statements)

References 68 publications

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“…Our data are in agreement with previous results obtained with TGFβ in collagen type I capillary morphogenesis of rat epididimal fat pad endothelial cells [27], and with those reported in fibrin gels for bovine aortic endothelial cells [28]. The similarity of results we have obtained with Matrigel matrix and Matrigel matrix GFR simplifies the interpretation of the data.…”

Section: Discussionsupporting

confidence: 92%

TGFβ1 antagonistic peptides inhibit TGFβ1-dependent angiogenesis

Serratì

Margheri

Pucci

et al. 2009

Biochemical Pharmacology

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The role of transforming growth factor-beta (TGF) in tumor promotion and in angiogenesis is context-dependent. While TGF prevents tumor growth and angiogenesis in early phases of tumor development, evidence is accumulating about its pro-angiogenic and tumor promotion activities in late stages of tumor progression. Here we have studied, in an experimental context previously reported to disclose the pro-

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Section: Discussionsupporting

confidence: 92%

TGFβ1 antagonistic peptides inhibit TGFβ1-dependent angiogenesis

Serratì

Margheri

Pucci

et al. 2009

Biochemical Pharmacology

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“…This type of difference between 2-and 3-dimensional models has already been described for transforming growth factor-␤1. 32 Among the mechanisms involved in OSM-induced endothelial cell proliferation, we observed that OSM stimulated the secretion of VEGF on HMEC-1s, a factor known to induce proliferation of endothelial cells. However, because LIF, which induces a proliferative effect, did not induce secretion of VEGF, we can assume that the proliferative effect of OSM is not totally due to the secretion of VEGF.…”

Section: Vasse Et Almentioning

confidence: 85%

Oncostatin M Induces Angiogenesis In Vitro and In Vivo

Vasse

Pourtau

Trochon

et al. 1999

ATVB

123

101

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Abstract-Neovascularization of the atherosclerotic plaque is responsible for its weakening and consequently for the complications of vascular disease. Macrophages are a source of growth factors that can modulate angiogenesis. In this study, we analyzed the effect of oncostatin M (OSM) on angiogenesis, as it could be involved in the development of atherosclerosis. The effect of OSM was compared with those of leukemia inhibitory factor (LIF) and interleukin-6 (IL-6). On human dermal microvasculature endothelial cells (HMEC-1s), OSM (22.5 to 112.5 pmol/L) induced a dose-dependent increase in cell proliferation greater than that induced by the classic angiogenic factors vascular endothelial growth factor (VEGF; 543 pmol/L) and basic fibroblast growth factor (bFGF; 1.1 nmol/L). LIF (19 to 475 pmol/L) induced only a 30% increase in cell proliferation, and IL-6 had no effect. Furthermore, in a modified Boyden-chamber model, OSM, LIF, and IL-6 were chemoattractant for HMEC-1s. In a tridimensional gel of fibrin, OSM increased tube formation and tube length, which were already noticeable by day 3. LIF and IL-6 induced a weaker effect that was only obvious by day 10. The angiogenic effect of OSM was also demonstrated in vivo in a rabbit corneal model: OSM was more potent than LIF, the length of the neovessels being longer with OSM than with LIF, whereas IL-6 was without effect. We tested factors that could be involved in the proliferative effect of OSM on HMEC-1s. OSM induced only a slight increase in the urokinase receptor and a 60% increase in VEGF secretion, whereas it does not modify IL-8 secretion or bFGF levels. The effect of OSM seems to depend on endothelial cell origin and cell species: OSM (up to 112.5 pmol/L) did not induce human umbilical vein endothelial cell proliferation and even had a small inhibitory effect (17%) on calf pulmonary artery endothelial cells. In conclusion, OSM induces an angiogenic effect on capillary endothelial cells, which could be, at least in part, implicated in pathological processes such as atherosclerosis or tumor growth. Key Words: angiogenesis Ⅲ atherosclerosis Ⅲ oncostatin M Ⅲ leukemia inhibitory factor Ⅲ vascular endothelial growth factor I t is now established that the functional role of the macrophage extends far beyond its originally recognized role as a scavenger cell. Monocytes in particular are recognized as angiogenesis effector cells that produce a number of growth stimulators and inhibitors, proteolytic enzymes, and cytokines that can influence 1 or more steps in the angiogenesis cascade. It has been shown that activated monocytes or their culture supernatants induce new capillary growth in vitro and angiogenesis in vivo. 1,2 However, recent evidence also suggests that capillary regression may be mediated by monocytes by producing antiangiogenic factors in vitro and in vivo. [3][4][5] Thus, macrophages could be involved in both stimulation and suppression of angiogenesis.Because macrophages reside at the sites of atherosclerotic plaques in the vessel wall and because the...

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“…Although our data are most consistent with a heterotetrameric (T␤RI) 2 (T␤RII) 2 receptor complex, and we have obtained similar results with several cell lines, there are suggestions in the literature that the stoichiometry of the complex may vary. For example, the ratio of T␤RI to T␤RII in microvascular endothelial cells was significantly higher in three-dimensional versus two-dimensional cultures, corresponding to increasing resistance to the anti-proliferative but not the matrix-inducing effects of TGF-␤ (35). In other cell types, including bone, the ratio of type I to type II receptors may also be important, particularly in differentiating growth inhibition from other effects of TGF-␤ (36 -38).…”

Section: Discussionmentioning

confidence: 99%

Transforming Growth Factor-β Induces Formation of a Dithiothreitol-resistant Type I/Type II Receptor Complex in Live Cells

Wells¹,

Gilboa²,

Sun³

et al. 1999

Journal of Biological Chemistry

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Transforming growth factor-␤ (TGF-␤) binds to and signals via two serine-threonine kinase receptors, the type I (T␤RI) and type II (T␤RII) receptors. We have used different and complementary techniques to study the physical nature and ligand dependence of the complex formed by T␤RI and T␤RII. Velocity centrifugation of endogenous receptors suggests that ligand-bound T␤RI and T␤RII form a heteromeric complex that is most likely a heterotetramer. Antibody-mediated immunofluorescence co-patching of epitope-tagged receptors provides the first evidence in live cells that T␤RI⅐T␤RII complex formation occurs at a low but measurable degree in the absence of ligand, increasing significantly after TGF-␤ binding. In addition, we demonstrate that pretreatment of cells with dithiothreitol, which inhibits the binding of TGF-␤ to T␤RI, does not prevent formation of the T␤RI⅐T␤RII complex, but increases its sensitivity to detergent and prevents TGF-␤-activated T␤RI from phosphorylating Smad3 in vitro. This indicates that either a specific conformation of the T␤RI⅐T␤RII complex, disrupted by dithiothreitol, or direct binding of TGF-␤ to T␤RI is required for signaling.The transforming growth factor-␤ (TGF-␤) 1 ligands are members of a large superfamily of cystine knot growth factors, which includes decapentaplegic (dpp) from Drosophila melanogaster as well as the Mü llerian-inhibiting substance and the activins and bone morphogenetic proteins from mammals. The TGF-␤s are important modulators of development, the extracellular matrix, and the immune response; they are potent growth inhibitors in many cell types, and their receptors and some downstream signaling elements are tumor suppressors (1-5).TGF-␤ signals through the sequential activation of two serine-threonine kinase cell surface receptors (6 -10), termed type I and type II (T␤RI and T␤RII). These two receptors physically associate to form a stable complex (8, 11). Several chimeric receptor systems have established that this complex is required for signaling (12-16). Whether it is preformed or ligand-induced is controversial. Isolation of a T␤RI⅐T␤RII complex from detergent lysates was possible only after pretreatment with TGF-␤ (9). Ligand-independent interactions between receptor cytoplasmic domains, however, have been detected in transfected COS cells and in the yeast two-hybrid system, 2 and work with TGF-␤2 (which requires both receptors to bind) suggests that at least a small percentage of the cell surface receptor population is in preformed complexes (9,(17)(18)(19). Data from experiments on the effect of DTT also raise questions about the role of ligand in the complex. Treatment of cells with DTT prevents TGF-␤ binding to T␤RI but not to T␤RII (8,20) and, in vitro, prevents formation of the T␤RI⅐T␤RII complex. 3The stoichiometry of the signaling complex is not known. T␤RI and T␤RII form ligand-independent homodimers in the endoplasmic reticulum and on the cell surface (21,22). The simplest model is that two homodimers form a heterotetrameric signaling complex induce...

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Modulation of transforming growth factor beta receptor levels on microvascular endothelial cells during in vitro angiogenesis.

Cited by 148 publications

References 68 publications

TGFβ1 antagonistic peptides inhibit TGFβ1-dependent angiogenesis

TGFβ1 antagonistic peptides inhibit TGFβ1-dependent angiogenesis

Oncostatin M Induces Angiogenesis In Vitro and In Vivo

Transforming Growth Factor-β Induces Formation of a Dithiothreitol-resistant Type I/Type II Receptor Complex in Live Cells

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