Oncogene Proteins

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Victor W M Van Hinsbergh - One of the best experts on this subject based on the ideXlab platform.

  • urokinase receptor expression on human microvascular endothelial cells is increased by hypoxia implications for capillary like tube formation in a fibrin matrix
    Blood, 2000
    Co-Authors: Marielle E Kroon, Bea Van Der Vecht, Pieter Koolwijk, Victor W M Van Hinsbergh
    Abstract:

    Hypoxia stimulates angiogenesis, the formation of new blood vessels. This study evaluates the direct effect of hypoxia (1% oxygen) on the angiogenic response of human microvascular endothelial cells (hMVECs) seeded on top of a 3-dimensional fibrin matrix, hMVECs stimulated with fibroblast growth factor-2 (FGF-2) or vascular endothelial growth factor (VEGF) together with tumor necrosis factor-α (TNF-α) formed 2- to 3-fold more tubular structures under hypoxic conditions than in normoxic (20% oxygen) conditions. In both conditions the in-growth of capillary-like tubular structures into fibrin required cell-bound urokinase-type plasminogen activator (uPA) and plasmin activities. The hypoxia-induced increase in tube formation was accompanied by a decrease in uPA accumulation in the conditioned medium. This decrease in uPA level was completely abolished by uPA receptor-blocking antibodies. During hypoxic culturing uPA receptor activity and messenger RNA (mRNA) were indeed increased. This increase and, as a consequence, an increase in plasmin formation contribute to the hypoxia-induced stimulation of tube formation. A possible contribution of VEGF-A to the increased formation under hypoxic conditions is unlikely because there was no increased VEGF-A expression detected under hypoxic conditions, and the hypoxia-induced tube formation by FGF-2 and TNF-α was not inhibited by soluble VEGFR-1 (sVEGFR-1), or by antibodies blocking VEGFR-2. Furthermore, although the α(v)-integrin subunit was enhanced by hypoxia, blocking antibodies against α(v)β3 and α(v)β5-integrins had no effect on hypoxia-induced tube formation. Hypoxia increases uPA association and the angiogenic response of human endothelial cells in a fibrin matrix; the increase in the uPA receptor is an important determinant in this process. (C) 2000 by The American Society of Hematology. Chemicals/CAS: fibrin, 9001-31-4; phorbol 13 acetate 12 myristate, 16561-29-8; plasmin, 9001-90-5, 9004-09-5; plasminogen activator, 9039-53-6; tissue plasminogen activator, 105913-11-9; urokinase, 139639-24-0; vasculotropin, 127464-60-2; Antigens, CD; Culture Media; Culture Media, Conditioned; DNA, Complementary; Endothelial Growth Factors; Fibrin, 9001-31-4; Fibroblast Growth Factor 2, 103107-01-3; Integrin alphaV; integrin alphaVbeta5; Integrins; Lymphokines; Oxygen, 7782-44-7; Plasmin, EC 3.4.21.7; plasminogen activator, urokinase receptors; Proto-Oncogene Proteins; Receptor Protein-Tyrosine Kinases, EC 2.7.1.112; Receptors, Cell Surface; Receptors, Growth Factor; Receptors, Vascular Endothelial Growth Factor, EC 2.7.1.112; Receptors, Vitronectin; RNA, Messenger; Tumor Necrosis Factor; Urinary Plasminogen Activator, EC 3.4.21.73; Vascular Endothelial Growth Factor Receptor-1, EC 2.7.1.112; vascular endothelial growth factor

  • urokinase receptor expression on human microvascular endothelial cells is increased by hypoxia implications for capillary like tube formation in a fibrin matrix
    Blood, 2000
    Co-Authors: Marielle E Kroon, Bea Van Der Vecht, Pieter Koolwijk, Victor W M Van Hinsbergh
    Abstract:

    Hypoxia stimulates angiogenesis, the formation of new blood vessels. This study evaluates the direct effect of hypoxia (1% oxygen) on the angiogenic response of human microvascular endothelial cells (hMVECs) seeded on top of a 3-dimensional fibrin matrix, hMVECs stimulated with fibroblast growth factor-2 (FGF-2) or vascular endothelial growth factor (VEGF) together with tumor necrosis factor-α (TNF-α) formed 2- to 3-fold more tubular structures under hypoxic conditions than in normoxic (20% oxygen) conditions. In both conditions the in-growth of capillary-like tubular structures into fibrin required cell-bound urokinase-type plasminogen activator (uPA) and plasmin activities. The hypoxia-induced increase in tube formation was accompanied by a decrease in uPA accumulation in the conditioned medium. This decrease in uPA level was completely abolished by uPA receptor-blocking antibodies. During hypoxic culturing uPA receptor activity and messenger RNA (mRNA) were indeed increased. This increase and, as a consequence, an increase in plasmin formation contribute to the hypoxia-induced stimulation of tube formation. A possible contribution of VEGF-A to the increased formation under hypoxic conditions is unlikely because there was no increased VEGF-A expression detected under hypoxic conditions, and the hypoxia-induced tube formation by FGF-2 and TNF-α was not inhibited by soluble VEGFR-1 (sVEGFR-1), or by antibodies blocking VEGFR-2. Furthermore, although the α(v)-integrin subunit was enhanced by hypoxia, blocking antibodies against α(v)β3 and α(v)β5-integrins had no effect on hypoxia-induced tube formation. Hypoxia increases uPA association and the angiogenic response of human endothelial cells in a fibrin matrix; the increase in the uPA receptor is an important determinant in this process. (C) 2000 by The American Society of Hematology. Chemicals/CAS: fibrin, 9001-31-4; phorbol 13 acetate 12 myristate, 16561-29-8; plasmin, 9001-90-5, 9004-09-5; plasminogen activator, 9039-53-6; tissue plasminogen activator, 105913-11-9; urokinase, 139639-24-0; vasculotropin, 127464-60-2; Antigens, CD; Culture Media; Culture Media, Conditioned; DNA, Complementary; Endothelial Growth Factors; Fibrin, 9001-31-4; Fibroblast Growth Factor 2, 103107-01-3; Integrin alphaV; integrin alphaVbeta5; Integrins; Lymphokines; Oxygen, 7782-44-7; Plasmin, EC 3.4.21.7; plasminogen activator, urokinase receptors; Proto-Oncogene Proteins; Receptor Protein-Tyrosine Kinases, EC 2.7.1.112; Receptors, Cell Surface; Receptors, Growth Factor; Receptors, Vascular Endothelial Growth Factor, EC 2.7.1.112; Receptors, Vitronectin; RNA, Messenger; Tumor Necrosis Factor; Urinary Plasminogen Activator, EC 3.4.21.73; Vascular Endothelial Growth Factor Receptor-1, EC 2.7.1.112; vascular endothelial growth factor

Marielle E Kroon - One of the best experts on this subject based on the ideXlab platform.

  • urokinase receptor expression on human microvascular endothelial cells is increased by hypoxia implications for capillary like tube formation in a fibrin matrix
    Blood, 2000
    Co-Authors: Marielle E Kroon, Bea Van Der Vecht, Pieter Koolwijk, Victor W M Van Hinsbergh
    Abstract:

    Hypoxia stimulates angiogenesis, the formation of new blood vessels. This study evaluates the direct effect of hypoxia (1% oxygen) on the angiogenic response of human microvascular endothelial cells (hMVECs) seeded on top of a 3-dimensional fibrin matrix, hMVECs stimulated with fibroblast growth factor-2 (FGF-2) or vascular endothelial growth factor (VEGF) together with tumor necrosis factor-α (TNF-α) formed 2- to 3-fold more tubular structures under hypoxic conditions than in normoxic (20% oxygen) conditions. In both conditions the in-growth of capillary-like tubular structures into fibrin required cell-bound urokinase-type plasminogen activator (uPA) and plasmin activities. The hypoxia-induced increase in tube formation was accompanied by a decrease in uPA accumulation in the conditioned medium. This decrease in uPA level was completely abolished by uPA receptor-blocking antibodies. During hypoxic culturing uPA receptor activity and messenger RNA (mRNA) were indeed increased. This increase and, as a consequence, an increase in plasmin formation contribute to the hypoxia-induced stimulation of tube formation. A possible contribution of VEGF-A to the increased formation under hypoxic conditions is unlikely because there was no increased VEGF-A expression detected under hypoxic conditions, and the hypoxia-induced tube formation by FGF-2 and TNF-α was not inhibited by soluble VEGFR-1 (sVEGFR-1), or by antibodies blocking VEGFR-2. Furthermore, although the α(v)-integrin subunit was enhanced by hypoxia, blocking antibodies against α(v)β3 and α(v)β5-integrins had no effect on hypoxia-induced tube formation. Hypoxia increases uPA association and the angiogenic response of human endothelial cells in a fibrin matrix; the increase in the uPA receptor is an important determinant in this process. (C) 2000 by The American Society of Hematology. Chemicals/CAS: fibrin, 9001-31-4; phorbol 13 acetate 12 myristate, 16561-29-8; plasmin, 9001-90-5, 9004-09-5; plasminogen activator, 9039-53-6; tissue plasminogen activator, 105913-11-9; urokinase, 139639-24-0; vasculotropin, 127464-60-2; Antigens, CD; Culture Media; Culture Media, Conditioned; DNA, Complementary; Endothelial Growth Factors; Fibrin, 9001-31-4; Fibroblast Growth Factor 2, 103107-01-3; Integrin alphaV; integrin alphaVbeta5; Integrins; Lymphokines; Oxygen, 7782-44-7; Plasmin, EC 3.4.21.7; plasminogen activator, urokinase receptors; Proto-Oncogene Proteins; Receptor Protein-Tyrosine Kinases, EC 2.7.1.112; Receptors, Cell Surface; Receptors, Growth Factor; Receptors, Vascular Endothelial Growth Factor, EC 2.7.1.112; Receptors, Vitronectin; RNA, Messenger; Tumor Necrosis Factor; Urinary Plasminogen Activator, EC 3.4.21.73; Vascular Endothelial Growth Factor Receptor-1, EC 2.7.1.112; vascular endothelial growth factor

  • urokinase receptor expression on human microvascular endothelial cells is increased by hypoxia implications for capillary like tube formation in a fibrin matrix
    Blood, 2000
    Co-Authors: Marielle E Kroon, Bea Van Der Vecht, Pieter Koolwijk, Victor W M Van Hinsbergh
    Abstract:

    Hypoxia stimulates angiogenesis, the formation of new blood vessels. This study evaluates the direct effect of hypoxia (1% oxygen) on the angiogenic response of human microvascular endothelial cells (hMVECs) seeded on top of a 3-dimensional fibrin matrix, hMVECs stimulated with fibroblast growth factor-2 (FGF-2) or vascular endothelial growth factor (VEGF) together with tumor necrosis factor-α (TNF-α) formed 2- to 3-fold more tubular structures under hypoxic conditions than in normoxic (20% oxygen) conditions. In both conditions the in-growth of capillary-like tubular structures into fibrin required cell-bound urokinase-type plasminogen activator (uPA) and plasmin activities. The hypoxia-induced increase in tube formation was accompanied by a decrease in uPA accumulation in the conditioned medium. This decrease in uPA level was completely abolished by uPA receptor-blocking antibodies. During hypoxic culturing uPA receptor activity and messenger RNA (mRNA) were indeed increased. This increase and, as a consequence, an increase in plasmin formation contribute to the hypoxia-induced stimulation of tube formation. A possible contribution of VEGF-A to the increased formation under hypoxic conditions is unlikely because there was no increased VEGF-A expression detected under hypoxic conditions, and the hypoxia-induced tube formation by FGF-2 and TNF-α was not inhibited by soluble VEGFR-1 (sVEGFR-1), or by antibodies blocking VEGFR-2. Furthermore, although the α(v)-integrin subunit was enhanced by hypoxia, blocking antibodies against α(v)β3 and α(v)β5-integrins had no effect on hypoxia-induced tube formation. Hypoxia increases uPA association and the angiogenic response of human endothelial cells in a fibrin matrix; the increase in the uPA receptor is an important determinant in this process. (C) 2000 by The American Society of Hematology. Chemicals/CAS: fibrin, 9001-31-4; phorbol 13 acetate 12 myristate, 16561-29-8; plasmin, 9001-90-5, 9004-09-5; plasminogen activator, 9039-53-6; tissue plasminogen activator, 105913-11-9; urokinase, 139639-24-0; vasculotropin, 127464-60-2; Antigens, CD; Culture Media; Culture Media, Conditioned; DNA, Complementary; Endothelial Growth Factors; Fibrin, 9001-31-4; Fibroblast Growth Factor 2, 103107-01-3; Integrin alphaV; integrin alphaVbeta5; Integrins; Lymphokines; Oxygen, 7782-44-7; Plasmin, EC 3.4.21.7; plasminogen activator, urokinase receptors; Proto-Oncogene Proteins; Receptor Protein-Tyrosine Kinases, EC 2.7.1.112; Receptors, Cell Surface; Receptors, Growth Factor; Receptors, Vascular Endothelial Growth Factor, EC 2.7.1.112; Receptors, Vitronectin; RNA, Messenger; Tumor Necrosis Factor; Urinary Plasminogen Activator, EC 3.4.21.73; Vascular Endothelial Growth Factor Receptor-1, EC 2.7.1.112; vascular endothelial growth factor

Shur-tzu Chen - One of the best experts on this subject based on the ideXlab platform.

  • Differential expression of β-amyloid precursor and Bcl-2 proto-Oncogene Proteins in the developing dog retina
    Neuroscience research, 1999
    Co-Authors: Shur-tzu Chen, Jiang-ping Wang, Chi-hsien Chien, Ching-liang Shen
    Abstract:

    Abstract Previous studies of rat retinas have not only provided evidence that β-amyloid precursor (APP) and B-cell lymphoma proto-Oncogene (Bcl-2) Proteins are colocalized in retinal Muller glial cells, but have also indicated that common mechanisms regulate their expression in these cells (Chen, S.T., Garey, L.J., Jen, L.S., 1994. Bcl-2 proto-Oncogene protein immunoreactivity in normally developing and axotomised rat retinas. Neurosci. Lett. 172, 11–14; Chen, S.T., Gentleman, S.M., Garey, L.J., Jen, L.S., 1996. Distribution of β-amyloid precursor and B-cell lymphoma proto-Oncogene Proteins in the rat retina after optic nerve transection or vascular lesion. J. Neuropathol. Exp. Neurol. 55, 1073–1082; Chen, S.T., Garey, L.J., Jen, L.S., 1997. Expression of β-amyloid precursor protein immunoreactivity in the retina of the rat during normal development and after neonatal optic tract lesion. NeuroReport 8, 713–717). This investigation attempts to resolve whether or not the pattern observed in rats also applies to other higher mammalian species by examining the expression of immunoreactivity to APP and Bcl-2 in developing as well as mature dog retinas using immunocytochemical methods. Experimental results indicate that the immunoreactivity of both APP and Bcl-2 is located primarily in the inner retina, particularly in the ganglion cells and their axons in late fetal and neonatal stages. From the second postnatal week (the time of eye opening) onwards, immunoreactivity to APP, but not Bcl-2, is localized primarily in the endfeet and proximal part of the radial process of retinal Muller glial cells. Although the findings show both APP and Bcl-2 are expressed in ganglion cells and their processes suggest that the molecules have a role in the differentiation of neurons in the central nervous tissue, the lack of Bcl-2 in the Muller glial cells in dog retinas further suggests that the two molecules may have different biological roles with respect to glial function.

  • Expression of β-amyloid precursor and Bcl-2 proto-Oncogene Proteins in rat retinas after intravitreal injection of aminoadipic acid
    Neurochemistry international, 1999
    Co-Authors: Shur-tzu Chen, Jiang-ping Wang, L.j. Garey, Ling Sun Jen
    Abstract:

    Abstract In order to investigate the role of glia in relation to factors that affect the expression of beta-amyloid precursor protein ( β APP) and B cell lymphoma Oncogene protein (Bcl-2) in the central nervous tissue, the patterns of expression of β APP and Bcl-2 in developing and mature rat retinas were studied immunocytochemically after intravitreal injection of alpha-aminoadipic acid ( α -AAA), a glutamate analogue and gliotoxin that is known to cause injury of retinal Muller glial cells. In normal developing retinas, β APP and Bcl-2 were expressed primarily but transiently in a small number of neurons in the ganglion cell layer during the first postnatal week. Immunoreactivity of β APP and Bcl-2 appeared in the endfeet and proximal part of the radial processes of Muller glial cells from the second postnatal week onwards. In rats that received intravitreal injection of α -AAA at birth, there was a loss of immunoreactivity to vimentin, and a delayed expressed on β APP or Bcl-2 in Muller glial cells until 3–5 weeks post-injection. Immunoreactive neurons were also observed in the inner retina especially in the ganglion cell layer from 5 to 35 days after injection. A significant reduction in numerical density of cells with large somata in the ganglion cell layer was observed in the neonatally injected retinas at P56, which was accompanied by an increased immunostaining in radial processes of Muller glial cells. In contrast, no detectable changes in the expression of β APP and Bcl-2 were observed in retina that received α -AAA as adults. These results indicate that the gliotoxin α -AAA has long lasting effects on the expression of β APP and Bcl-2 in Muller glial cells as well as neurons in the developing but not mature retinas. The loss of vimentin and delayed expression of β APP and Bcl-2 in developing Muller glial cells suggests that the metabolic integrity of Muller cells was temporarily compromised, which may have adverse effects on developing neurons that are vulnerable or dependent on trophic support from the Muller glial cells.

Pieter Koolwijk - One of the best experts on this subject based on the ideXlab platform.

  • urokinase receptor expression on human microvascular endothelial cells is increased by hypoxia implications for capillary like tube formation in a fibrin matrix
    Blood, 2000
    Co-Authors: Marielle E Kroon, Bea Van Der Vecht, Pieter Koolwijk, Victor W M Van Hinsbergh
    Abstract:

    Hypoxia stimulates angiogenesis, the formation of new blood vessels. This study evaluates the direct effect of hypoxia (1% oxygen) on the angiogenic response of human microvascular endothelial cells (hMVECs) seeded on top of a 3-dimensional fibrin matrix, hMVECs stimulated with fibroblast growth factor-2 (FGF-2) or vascular endothelial growth factor (VEGF) together with tumor necrosis factor-α (TNF-α) formed 2- to 3-fold more tubular structures under hypoxic conditions than in normoxic (20% oxygen) conditions. In both conditions the in-growth of capillary-like tubular structures into fibrin required cell-bound urokinase-type plasminogen activator (uPA) and plasmin activities. The hypoxia-induced increase in tube formation was accompanied by a decrease in uPA accumulation in the conditioned medium. This decrease in uPA level was completely abolished by uPA receptor-blocking antibodies. During hypoxic culturing uPA receptor activity and messenger RNA (mRNA) were indeed increased. This increase and, as a consequence, an increase in plasmin formation contribute to the hypoxia-induced stimulation of tube formation. A possible contribution of VEGF-A to the increased formation under hypoxic conditions is unlikely because there was no increased VEGF-A expression detected under hypoxic conditions, and the hypoxia-induced tube formation by FGF-2 and TNF-α was not inhibited by soluble VEGFR-1 (sVEGFR-1), or by antibodies blocking VEGFR-2. Furthermore, although the α(v)-integrin subunit was enhanced by hypoxia, blocking antibodies against α(v)β3 and α(v)β5-integrins had no effect on hypoxia-induced tube formation. Hypoxia increases uPA association and the angiogenic response of human endothelial cells in a fibrin matrix; the increase in the uPA receptor is an important determinant in this process. (C) 2000 by The American Society of Hematology. Chemicals/CAS: fibrin, 9001-31-4; phorbol 13 acetate 12 myristate, 16561-29-8; plasmin, 9001-90-5, 9004-09-5; plasminogen activator, 9039-53-6; tissue plasminogen activator, 105913-11-9; urokinase, 139639-24-0; vasculotropin, 127464-60-2; Antigens, CD; Culture Media; Culture Media, Conditioned; DNA, Complementary; Endothelial Growth Factors; Fibrin, 9001-31-4; Fibroblast Growth Factor 2, 103107-01-3; Integrin alphaV; integrin alphaVbeta5; Integrins; Lymphokines; Oxygen, 7782-44-7; Plasmin, EC 3.4.21.7; plasminogen activator, urokinase receptors; Proto-Oncogene Proteins; Receptor Protein-Tyrosine Kinases, EC 2.7.1.112; Receptors, Cell Surface; Receptors, Growth Factor; Receptors, Vascular Endothelial Growth Factor, EC 2.7.1.112; Receptors, Vitronectin; RNA, Messenger; Tumor Necrosis Factor; Urinary Plasminogen Activator, EC 3.4.21.73; Vascular Endothelial Growth Factor Receptor-1, EC 2.7.1.112; vascular endothelial growth factor

  • urokinase receptor expression on human microvascular endothelial cells is increased by hypoxia implications for capillary like tube formation in a fibrin matrix
    Blood, 2000
    Co-Authors: Marielle E Kroon, Bea Van Der Vecht, Pieter Koolwijk, Victor W M Van Hinsbergh
    Abstract:

    Hypoxia stimulates angiogenesis, the formation of new blood vessels. This study evaluates the direct effect of hypoxia (1% oxygen) on the angiogenic response of human microvascular endothelial cells (hMVECs) seeded on top of a 3-dimensional fibrin matrix, hMVECs stimulated with fibroblast growth factor-2 (FGF-2) or vascular endothelial growth factor (VEGF) together with tumor necrosis factor-α (TNF-α) formed 2- to 3-fold more tubular structures under hypoxic conditions than in normoxic (20% oxygen) conditions. In both conditions the in-growth of capillary-like tubular structures into fibrin required cell-bound urokinase-type plasminogen activator (uPA) and plasmin activities. The hypoxia-induced increase in tube formation was accompanied by a decrease in uPA accumulation in the conditioned medium. This decrease in uPA level was completely abolished by uPA receptor-blocking antibodies. During hypoxic culturing uPA receptor activity and messenger RNA (mRNA) were indeed increased. This increase and, as a consequence, an increase in plasmin formation contribute to the hypoxia-induced stimulation of tube formation. A possible contribution of VEGF-A to the increased formation under hypoxic conditions is unlikely because there was no increased VEGF-A expression detected under hypoxic conditions, and the hypoxia-induced tube formation by FGF-2 and TNF-α was not inhibited by soluble VEGFR-1 (sVEGFR-1), or by antibodies blocking VEGFR-2. Furthermore, although the α(v)-integrin subunit was enhanced by hypoxia, blocking antibodies against α(v)β3 and α(v)β5-integrins had no effect on hypoxia-induced tube formation. Hypoxia increases uPA association and the angiogenic response of human endothelial cells in a fibrin matrix; the increase in the uPA receptor is an important determinant in this process. (C) 2000 by The American Society of Hematology. Chemicals/CAS: fibrin, 9001-31-4; phorbol 13 acetate 12 myristate, 16561-29-8; plasmin, 9001-90-5, 9004-09-5; plasminogen activator, 9039-53-6; tissue plasminogen activator, 105913-11-9; urokinase, 139639-24-0; vasculotropin, 127464-60-2; Antigens, CD; Culture Media; Culture Media, Conditioned; DNA, Complementary; Endothelial Growth Factors; Fibrin, 9001-31-4; Fibroblast Growth Factor 2, 103107-01-3; Integrin alphaV; integrin alphaVbeta5; Integrins; Lymphokines; Oxygen, 7782-44-7; Plasmin, EC 3.4.21.7; plasminogen activator, urokinase receptors; Proto-Oncogene Proteins; Receptor Protein-Tyrosine Kinases, EC 2.7.1.112; Receptors, Cell Surface; Receptors, Growth Factor; Receptors, Vascular Endothelial Growth Factor, EC 2.7.1.112; Receptors, Vitronectin; RNA, Messenger; Tumor Necrosis Factor; Urinary Plasminogen Activator, EC 3.4.21.73; Vascular Endothelial Growth Factor Receptor-1, EC 2.7.1.112; vascular endothelial growth factor

Bea Van Der Vecht - One of the best experts on this subject based on the ideXlab platform.

  • urokinase receptor expression on human microvascular endothelial cells is increased by hypoxia implications for capillary like tube formation in a fibrin matrix
    Blood, 2000
    Co-Authors: Marielle E Kroon, Bea Van Der Vecht, Pieter Koolwijk, Victor W M Van Hinsbergh
    Abstract:

    Hypoxia stimulates angiogenesis, the formation of new blood vessels. This study evaluates the direct effect of hypoxia (1% oxygen) on the angiogenic response of human microvascular endothelial cells (hMVECs) seeded on top of a 3-dimensional fibrin matrix, hMVECs stimulated with fibroblast growth factor-2 (FGF-2) or vascular endothelial growth factor (VEGF) together with tumor necrosis factor-α (TNF-α) formed 2- to 3-fold more tubular structures under hypoxic conditions than in normoxic (20% oxygen) conditions. In both conditions the in-growth of capillary-like tubular structures into fibrin required cell-bound urokinase-type plasminogen activator (uPA) and plasmin activities. The hypoxia-induced increase in tube formation was accompanied by a decrease in uPA accumulation in the conditioned medium. This decrease in uPA level was completely abolished by uPA receptor-blocking antibodies. During hypoxic culturing uPA receptor activity and messenger RNA (mRNA) were indeed increased. This increase and, as a consequence, an increase in plasmin formation contribute to the hypoxia-induced stimulation of tube formation. A possible contribution of VEGF-A to the increased formation under hypoxic conditions is unlikely because there was no increased VEGF-A expression detected under hypoxic conditions, and the hypoxia-induced tube formation by FGF-2 and TNF-α was not inhibited by soluble VEGFR-1 (sVEGFR-1), or by antibodies blocking VEGFR-2. Furthermore, although the α(v)-integrin subunit was enhanced by hypoxia, blocking antibodies against α(v)β3 and α(v)β5-integrins had no effect on hypoxia-induced tube formation. Hypoxia increases uPA association and the angiogenic response of human endothelial cells in a fibrin matrix; the increase in the uPA receptor is an important determinant in this process. (C) 2000 by The American Society of Hematology. Chemicals/CAS: fibrin, 9001-31-4; phorbol 13 acetate 12 myristate, 16561-29-8; plasmin, 9001-90-5, 9004-09-5; plasminogen activator, 9039-53-6; tissue plasminogen activator, 105913-11-9; urokinase, 139639-24-0; vasculotropin, 127464-60-2; Antigens, CD; Culture Media; Culture Media, Conditioned; DNA, Complementary; Endothelial Growth Factors; Fibrin, 9001-31-4; Fibroblast Growth Factor 2, 103107-01-3; Integrin alphaV; integrin alphaVbeta5; Integrins; Lymphokines; Oxygen, 7782-44-7; Plasmin, EC 3.4.21.7; plasminogen activator, urokinase receptors; Proto-Oncogene Proteins; Receptor Protein-Tyrosine Kinases, EC 2.7.1.112; Receptors, Cell Surface; Receptors, Growth Factor; Receptors, Vascular Endothelial Growth Factor, EC 2.7.1.112; Receptors, Vitronectin; RNA, Messenger; Tumor Necrosis Factor; Urinary Plasminogen Activator, EC 3.4.21.73; Vascular Endothelial Growth Factor Receptor-1, EC 2.7.1.112; vascular endothelial growth factor

  • urokinase receptor expression on human microvascular endothelial cells is increased by hypoxia implications for capillary like tube formation in a fibrin matrix
    Blood, 2000
    Co-Authors: Marielle E Kroon, Bea Van Der Vecht, Pieter Koolwijk, Victor W M Van Hinsbergh
    Abstract:

    Hypoxia stimulates angiogenesis, the formation of new blood vessels. This study evaluates the direct effect of hypoxia (1% oxygen) on the angiogenic response of human microvascular endothelial cells (hMVECs) seeded on top of a 3-dimensional fibrin matrix, hMVECs stimulated with fibroblast growth factor-2 (FGF-2) or vascular endothelial growth factor (VEGF) together with tumor necrosis factor-α (TNF-α) formed 2- to 3-fold more tubular structures under hypoxic conditions than in normoxic (20% oxygen) conditions. In both conditions the in-growth of capillary-like tubular structures into fibrin required cell-bound urokinase-type plasminogen activator (uPA) and plasmin activities. The hypoxia-induced increase in tube formation was accompanied by a decrease in uPA accumulation in the conditioned medium. This decrease in uPA level was completely abolished by uPA receptor-blocking antibodies. During hypoxic culturing uPA receptor activity and messenger RNA (mRNA) were indeed increased. This increase and, as a consequence, an increase in plasmin formation contribute to the hypoxia-induced stimulation of tube formation. A possible contribution of VEGF-A to the increased formation under hypoxic conditions is unlikely because there was no increased VEGF-A expression detected under hypoxic conditions, and the hypoxia-induced tube formation by FGF-2 and TNF-α was not inhibited by soluble VEGFR-1 (sVEGFR-1), or by antibodies blocking VEGFR-2. Furthermore, although the α(v)-integrin subunit was enhanced by hypoxia, blocking antibodies against α(v)β3 and α(v)β5-integrins had no effect on hypoxia-induced tube formation. Hypoxia increases uPA association and the angiogenic response of human endothelial cells in a fibrin matrix; the increase in the uPA receptor is an important determinant in this process. (C) 2000 by The American Society of Hematology. Chemicals/CAS: fibrin, 9001-31-4; phorbol 13 acetate 12 myristate, 16561-29-8; plasmin, 9001-90-5, 9004-09-5; plasminogen activator, 9039-53-6; tissue plasminogen activator, 105913-11-9; urokinase, 139639-24-0; vasculotropin, 127464-60-2; Antigens, CD; Culture Media; Culture Media, Conditioned; DNA, Complementary; Endothelial Growth Factors; Fibrin, 9001-31-4; Fibroblast Growth Factor 2, 103107-01-3; Integrin alphaV; integrin alphaVbeta5; Integrins; Lymphokines; Oxygen, 7782-44-7; Plasmin, EC 3.4.21.7; plasminogen activator, urokinase receptors; Proto-Oncogene Proteins; Receptor Protein-Tyrosine Kinases, EC 2.7.1.112; Receptors, Cell Surface; Receptors, Growth Factor; Receptors, Vascular Endothelial Growth Factor, EC 2.7.1.112; Receptors, Vitronectin; RNA, Messenger; Tumor Necrosis Factor; Urinary Plasminogen Activator, EC 3.4.21.73; Vascular Endothelial Growth Factor Receptor-1, EC 2.7.1.112; vascular endothelial growth factor

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