Vascular Endothelial Growth Factor Activates STAT Proteins in Aortic Endothelial Cells

Bartoli, Manuela; Gu, Xiaocheng; Tsai, Nai Tse; Venema, Richard C.; Brooks, Steven E.; Marrero, Mario B.; Caldwell, Ruth B.

doi:10.1074/jbc.c000318200

Cited by 128 publications

(120 citation statements)

References 40 publications

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“…STAT3 has been implicated in the stimulation of angiogenesis by inducing VEGF expression (for review, see Chen and Han, 2007). In addition, VEGF induces activation of STAT3 and promotes its autocrine expression in RECs (Bartoli et al, 2000;Bartoli et al, 2003). Of interest, STAT3 activation is stimulated by inflammatory pathways (Hirano et al, 2000).…”

Section: Transcriptional Regulation Of Vegf Expression-tissuementioning

confidence: 99%

Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

612

527

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Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the U.S., for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF), a 40 kDa dimeric glycoprotein, promotes angiogenesis in each of these conditions, making it a highly significant therapeutic target. However, VEGF is pleiotropic, affecting a broad spectrum of endothelial, neuronal and glial behaviors, and confounding the validity of anti-VEGF strategies, particularly under chronic disease conditions. In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability in a wide variety of biological contexts. This article will describe the roles played by VEGF in the pathogenesis of retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. The potential disadvantages of inhibiting VEGF will be discussed, as will the rationales for targeting other VEGF-related modulators of angiogenesis.

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Section: Transcriptional Regulation Of Vegf Expression-tissuementioning

confidence: 99%

Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

612

527

View full text Add to dashboard Cite

show abstract

“…19,20 In brief, protein samples (50 mg) were added to wells of a 96-well plate coated with VEGF antibody, incubated at 41C overnight, and processed according to the manufacturer's instruction (RayBiotech, Inc, Atlanta, GA, USA). Absorbance was measured in a plate reader at 450 nm.…”

Section: Examination Of the Vegf Protein By Elisamentioning

confidence: 99%

High glucose attenuates insulin-induced VEGF expression in bovine retinal microvascular endothelial cells

Xia

Jiang

et al. 2009

Eye

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“…Stat5a and Stat5b in hematopoietic cells seem to promote growth, inhibit apoptosis, and may be involved in malignant transformation (Matsumura et al, 1999;Nosaka et al, 1999;Demoulin et al, 2000), and are also essential mediators of the effects of prolactin (PRL) and growth hormone (GH) as well as IL-2 and other cytokines (Groner and Gouilleux, 1995;Grimley et al, 1999;Moriggl et al, 1999;Herrington et al, 2000;Lin and Leonard, 2000). However, although STAT proteins in some cells have been found to be phosphorylated and activated in response to growth factors, including EGF (Ruff-Jamison et al, 1993Richer et al, 1998;Guren et al, 1999;Luetteke et al, 1999;Olayioye et al, 1999), PDGF (Valgeirsdottir et al, 1998;Sachsenmaier et al, 1999), and VEGF (Bartoli et al, 2000), their exact function in receptor tyrosine kinase signaling has not been defined, and the role of STAT proteins in EGF receptor-mediated mitogenic mechanisms is not known.…”

mentioning

confidence: 99%

EGF receptor‐mediated, c‐Src‐dependent, activation of Stat5b is downregulated in mitogenically responsive hepatocytes

Guren

Ødegård

Abrahamsen

et al. 2003

Journal Cellular Physiology

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Signal transducer and activator of transcription (STAT) proteins may be activated by epidermal growth factor (EGF), but their role in EGF receptor-mediated mitogenic signaling is not clear. We previously showed that Stat5b was activated by EGF in rat hepatocytes in primary monolayer culture. In the present study, we found that EGF induced tyrosine phosphorylation of Stat5b both on Tyr-699, which correlated with specific DNA binding activity, and also on other tyrosine residues. The Src tyrosine kinase inhibitor CGP77675 blocked the EGF-induced activation of Stat5b, but did not affect the Stat5b activation by growth hormone (GH) or prolactin (PRL). The Stat5b response to EGF was most pronounced soon (3 h) after plating (early G 1 ) and at high cell density (50,000 hepatocytes per cm 2 ). However, at this cell density EGF did not stimulate DNA synthesis. In hepatocytes at 24 h of culturing (mid/late G 1 ) with 20,000 cells per cm 2 , EGF induced strong phosphorylation of the EGF receptor, as well as Shc and ERK, and stimulated DNA synthesis, but did not activate Stat5b, although the Stat5b response to GH or PRL was retained. A strong GHinduced Stat5b activation neither influenced the DNA synthesis alone nor enhanced the mitogenic effect of EGF. The results show that EGF induces tyrosine phosphorylation and DNA-binding activity of Stat5b in a manner different from GH and PRL, apparently by a Src-dependent mechanism. The data also provide further evidence that Stat5b is not required for mitogenic signaling from the EGF receptor.

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Vascular Endothelial Growth Factor Activates STAT Proteins in Aortic Endothelial Cells

Cited by 128 publications

References 40 publications

Vascular endothelial growth factor in eye disease

Vascular endothelial growth factor in eye disease

High glucose attenuates insulin-induced VEGF expression in bovine retinal microvascular endothelial cells

EGF receptor‐mediated, c‐Src‐dependent, activation of Stat5b is downregulated in mitogenically responsive hepatocytes

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