scholarly journals Flow-Responsive Vascular Endothelial Growth Factor Receptor-Protein Kinase C Isoform Epsilon Signaling Mediates Glycolytic Metabolites for Vascular Repair

2018 ◽  
Vol 28 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Kyung In Baek ◽  
Rongsong Li ◽  
Nelson Jen ◽  
Howard Choi ◽  
Amir Kaboodrangi ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Growth Factor Receptor ◽  
Receptor Protein ◽  
Vascular Endothelial ◽  
Vascular Repair ◽  
Kinase C ◽  
Endothelial Growth Factor

scholarly journals Vascular Endothelial Growth Factor A Signaling Promotes Spinal Central Sensitization and Pain-related Behaviors in Female Rats with Bone Cancer

2019 ◽  
Vol 131 (5) ◽  
pp. 1125-1147 ◽  
Author(s):  
Xue-Ming Hu ◽  
Wei Yang ◽  
Li-Xia Du ◽  
Wen-Qiang Cui ◽  
Wen-Li Mi ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Protein Kinase C ◽  
Growth Factor ◽  
Cancer Pain ◽  
Growth Factor Receptor ◽  
Bone Cancer ◽  
Bone Cancer Pain ◽  
Vascular Endothelial ◽  
Kinase C ◽  
Endothelial Growth Factor

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Cancer pain is a pervasive clinical symptom impairing life quality. Vascular endothelial growth factor A has been well studied in tumor angiogenesis and is recognized as a therapeutic target for anti-cancer treatment. This study tested the hypothesis that vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 contribute to bone cancer pain regulation associated with spinal central sensitization. Methods This study was performed on female rats using a metastatic breast cancer bone pain model. Nociceptive behaviors were evaluated by mechanical allodynia, thermal hyperalgesia, spontaneous pain, and CatWalk gait analysis. Expression levels were measured by real-time quantitative polymerase chain reaction, western blot, and immunofluorescence analysis. Excitatory synaptic transmission was detected by whole-cell patch-clamp recordings. The primary outcome was the effect of pharmacologic intervention of spinal vascular endothelial growth factor A/vascular endothelial growth factor receptor 2–signaling on bone cancer pain behaviors. Results The mRNA and protein expression of vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 were upregulated in tumor-bearing rats. Spinal blocking vascular endothelial growth factor A or vascular endothelial growth factor receptor 2 significantly attenuated tumor-induced mechanical allodynia (mean ± SD: vascular endothelial growth factor A, 7.6 ± 2.6 g vs. 5.3 ± 3.3 g; vascular endothelial growth factor receptor 2, 7.8 ± 3.0 g vs. 5.2 ± 3.4 g; n = 6; P < 0.0001) and thermal hyperalgesia (mean ± SD: vascular endothelial growth factor A, 9.0 ± 2.4 s vs. 7.4 ± 2.7 s; vascular endothelial growth factor receptor 2, 9.3 ± 2.5 s vs. 7.5 ± 3.1 s; n = 6; P < 0.0001), as well as spontaneous pain and abnormal gaits. Exogenous vascular endothelial growth factor A enhanced excitatory synaptic transmission in a vascular endothelial growth factor receptor 2–dependent manner, and spinal injection of exogenous vascular endothelial growth factor A was sufficient to cause pain hypersensitivity via vascular endothelial growth factor receptor 2–mediated activation of protein kinase C and Src family kinase in naïve rats. Moreover, spinal blocking vascular endothelial growth factor A/vascular endothelial growth factor receptor 2 pathways suppressed protein kinase C-mediated N-methyl-d-aspartate receptor activation and Src family kinase-mediated proinflammatory cytokine production. Conclusions Vascular endothelial growth factor A/vascular endothelial growth factor receptor 2 contributes to central sensitization and bone cancer pain via activation of neuronal protein kinase C and microglial Src family kinase pathways in the spinal cord.

Vascular Endothelial Growth Factor Enhances the Expression of Urokinase Receptor in Human Endothelial Cells via Protein Kinase C Activation

2001 ◽  
Vol 85 (02) ◽  
pp. 296-302 ◽  
Author(s):  
Marielle Kroon ◽  
Pieter Koolwijk ◽  
Mario Vermeer ◽  
Bea van der Vecht ◽  
Victor van Hinsbergh
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Receptor Expression ◽  
Vascular Endothelial ◽  
Human Endothelial Cells ◽  
Kinase C ◽  
Endothelial Growth Factor

SummaryAmong other proteolytic enzymes, the urokinase-type plasminogen activator (u-PA)/plasmin cascade contributes to cell migration and the formation of capillary-like structures in a fibrinous exudate. The u-PA receptor (u-PAR) focuses proteolytical activity on the cell surface of the endothelial cell and hereby accelerates the pericellular matrix degradation. Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF)-2 enhance u-PA receptor expression in human endothelial cells. In this paper we show that the protein kinase C (PKC) inhibitors Ro31-8220 and GF109203X inhibit VEGF165-induced u-PAR antigen expression in human endothelial cells, whereas PKC inhibition had no effect on FGF-2-induced u-PAR antigen enhancement. In addition, inhibition of PKC activity had no effect on VEGF165-or FGF-2-induced proliferation in human endothelial cells. We conclude that VEGF165 induces u-PAR via a PKC-dependent pathway, whereas proliferation is induced via a different pathway probably involving tyrosine phosphorylation of proteins downstream of the VEGF receptors.

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