Vascular endothelial growth factor induces chemotaxis and proliferation of microglial cells

Forstreuter, Frauke; Lucius, Ralph; Mentlein, Rolf

doi:10.1016/s0165-5728(02)00315-6

Cited by 163 publications

(118 citation statements)

References 26 publications

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“…Of note, previous studies found that VEGF also induced a small reduction in AKT phosphorylation in microglial cells, which, like podocytes, express VEGF-R1 but not VEGF-R2 (13). It is possible that in the presence of nephrin, AKT phosphorylation is constitutively active in serum-starved, normal podocytes, supported by the observation that serum- starved levels of phospho-AKT are much higher in normal podocytes than nephrin-deficient cells.…”

Section: Discussionmentioning

confidence: 78%

“…In systemic endothelial cells, VEGF is known to stimulate a survival pathway through the phosphorylation of VEGF-R2, which results in phosphorylation of AKT at serine 473 and the upregulation of the antiapoptotic protein Bcl-2 (15). Survival signaling through VEGF-R1 or neuropilin in cells that do not express VEGF-R2, e.g., microglial cells (13), monocytes (8), and breast cancer cells (1), appears less well defined, in that in some cells [e.g., microglial cells (13)] phosphorylated AKT is not increased, but in others it appears to be required (1). Some recent reports also show that VEGF-R1 agonists can stimulate AKT phosphorylation and reduce apoptosis in endothelial cells (7) expressing both receptors.…”

mentioning

confidence: 99%

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Vascular endothelial growth factor and nephrin interact and reduce apoptosis in human podocytes

Foster¹,

Saleem²,

Mathieson³

et al. 2005

American Journal of Physiology-Renal Physiology

112

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Vascular endothelial growth factor (VEGF) is anti-cytotoxic in podocytes. Moreover, it has been suggested that nephrin, a cell adhesion molecule of the podocyte slit diaphragm, can contribute to antiapoptotic mechanisms in these cells. We therefore investigated whether VEGF signals to reduce apoptosis and the role of nephrin in this survival mechanism. Flow cytometry showed that podocytes with nephrin mutations had a significantly greater proportion of apoptosis. Although VEGF reduced apoptosis in human conditionally immortalized podocytes [wild-type (WT)] by 18.1% of control ( P < 0.001), it was unable to do so in nephrin-deficient human conditionally immortalized podocytes. Moreover, Western blotting and immunodetection with an anti-nephrin antibody showed that the phosphorylation of nephrin, compared with serum-starved WTs, was significantly increased (ratio of 3.36 ± 1.2 to control, P < 0.05) by VEGF treatment and significantly reduced by treatment with a neutralizing VEGF monoclonal antibody (mAb) (ratio of 0.2 ± 0.09 to control, P < 0.05). The AKT signaling pathway has been implicated in nephrin-mediated inhibition of apoptosis in transfected cells, but the role of this pathway has not previously been shown in podocytes. Surprisingly, exogenous VEGF decreased AKT/PKB phosphorylation in normal podocytes but increased it in nephrin-deficient podocytes. We suggest therefore that both exogenous and endogenous (podocyte derived) VEGF can stimulate the phosphorylation of nephrin and through this action may prevent podocyte apoptosis. However, the involvement of AKT in this survival response in normal human podocytes is not clear.

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Section: Discussionmentioning

confidence: 78%

mentioning

confidence: 99%

Vascular endothelial growth factor and nephrin interact and reduce apoptosis in human podocytes

Foster¹,

Saleem²,

Mathieson³

et al. 2005

American Journal of Physiology-Renal Physiology

112

View full text Add to dashboard Cite

show abstract

“…Again, VEGF receptors have been identified in retinal neurons, glia, microglia and RPE (Forstreuter et al, 2002;Hollborn et al, 2006;Robinson et al, 2001), and VEGF has been shown to play a key role in retinal development and survival of retinal neurons following ischemia/reperfusion injury (Nishijima et al, 2007;Yang and Cepko, 1996). As has been explained above, diabetes/high glucose stimulates increases in VEGF expression, and agents that block VEGF activity can prevent diabetes-induced retinal damage.…”

Section: Vegf and Diabetic Retinopathymentioning

confidence: 95%

Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

615

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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“…A dynamic relationship forms between the pre-neoplastic/ neoplastic and non-neoplastic stromal cell populations through stromagen and gliomagens release, which together facilitate tumorigenesis, tumor maintenance and glioma progression. endothelial growth factor (Forstreuter et al, 2002;Kerber et al, 2008), hepatocyte growth factor (Badie et al, 1999;Kunkel et al, 2001), monocyte chemoattractant protein-1 (Martinet et al, 1992;Leung et al, 1997) and the chemokine CX3CL1 (fractalkine) through activation of the CX3CR1 receptor (Held-Feindt et al, 2010). Monocyte chemoattractant protein-1 can also increase the surface expression of CX3CR1 on microglia (Green et al, 2006), thus providing amplification circuits for further microglia recruitment.…”

Section: Stromal Determinants Of Glioma Formation and Growthmentioning

confidence: 99%

The ecology of brain tumors: lessons learned from neurofibromatosis-1

Pong

Gutmann

2010

Oncogene

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Traditionally, cancer studies have primarily focused on mutations that activate growth or survival pathways in susceptible pre-neoplastic/neoplastic cells. However, recent research has revealed a critical role for nonneoplastic cells within the tumor microenvironment in the process of cancer formation and progression. In addition, the existence of regional and developmental variations in susceptible cell types and supportive microenvironments support a model of tumorigenesis in which the dynamic symbiotic relationship between neoplastic and non-neoplastic cell types dictate where and when cancers form and grow. In this review, we highlight advances in neurofibromatosis type 1 (NF1) genetically engineered mouse brain tumor (glioma) modeling to reveal how cellular and molecular heterogeneity in both the pre-neoplastic/ neoplastic and non-neoplastic cellular compartments contribute to gliomagenesis and glioma growth.

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Vascular endothelial growth factor induces chemotaxis and proliferation of microglial cells

Cited by 163 publications

References 26 publications

Vascular endothelial growth factor and nephrin interact and reduce apoptosis in human podocytes

Vascular endothelial growth factor and nephrin interact and reduce apoptosis in human podocytes

Vascular endothelial growth factor in eye disease

The ecology of brain tumors: lessons learned from neurofibromatosis-1

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