Osteopontin Induced Vascular Endothelial Growth Factor Production in Dispersed Nasal Polyp Cells through the Phosphatidylinositol 3-Kinase–Protein Kinase B and the Extracellular Signal-Regulated Kinase 1/2 Pathways

2017 ◽  
Vol 31 (4) ◽  
pp. e35-e41 ◽  
Author(s):  
Jingdong Du ◽  
Huadong Mao ◽  
Hong Ouyang ◽  
Yan Xin
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Protein Kinase B ◽  
Vascular Endothelial ◽  
Phosphatidylinositol 3 Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
Protein Levels ◽  
Extracellular Signal ◽  
Endothelial Growth Factor ◽  
Normal Controls

Background Osteopontin (OPN) is involved in cell survival, migration, and angiogenesis. The role of OPN in inducing angiogenesis in tumor has been confirmed. In this study, we investigated the expression of OPN in patients with chronic rhinosinusitis (CRS) with nasal polyp (NP) and the relationship of OPN with vascular endothelial growth factor (VEGF) production. Methods We enrolled 45 subjects with CRS (25 with CRS with NPs [CRSwNP] and 20 subjects with CRS without NPs [CRSsNP]), and with 14 normal controls to determine the expression of OPN and VEGF. The distribution, messenger RNA (mRNA), and protein levels of OPN and VEGF were examined by immunohistochemistry, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. The effect of OPN on the VEGF production was tested in dispersed NP cells (DNPC) and the involved signaling pathways were examined by Western blot. Results In NP tissue of the subjects with CRSwNP, the epithelial cells, interstitial cells, glandular cells, and endothelial cells were positive for OPN and VEGF staining, whereas OPN and VEGF immunoactivity in specimens of subjects with CRSsNP and in normal controls was significantly reduced. We found that the immunostainings, the mRNA expression, and the protein levels of OPN and VEGF were significantly increased in NPs compared with normal controls. OPN induced VEGF production by DNPCs in a time- and dose-dependent manner through phosphatidylinositol 3-kinase- protein kinase B and the extracellular signal-regulated kinase 1/2 pathway. Moreover, VEGF also induced OPN production, which formed a positive feedback between OPN and VEGF. Conclusion Our findings demonstrated that OPN and VEGF were overproduced in NPs and that OPN induced VEGF production, which indicated that OPN-VEGF axis might contribute to angiogenesis in NPs.

scholarly journals Gamma-irradiated β-glucan modulates signaling molecular targets of hepatocellular carcinoma in rats

Tumor Biology ◽  
2017 ◽  
Vol 39 (8) ◽  
pp. 101042831770870 ◽  
Author(s):  
Sawsan M Elsonbaty ◽  
Walid E Zahran ◽  
Fatma SM Moawed
Keyword(s):  
Hepatocellular Carcinoma ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factors ◽  
Growth Factor ◽  
Biological Response ◽  
Treated Group ◽  
Vascular Endothelial ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Endothelial Growth Factor

β-glucans are one of the most abundant forms of polysaccharides known as biological response modifiers which influence host’s biological response and stimulate immune system. Accordingly, this study was initiated to evaluate irradiated β-glucan as a modulator for cellular signaling growth factors involved in the pathogenesis of hepatocellular carcinoma in rats. Hepatocellular carcinoma was induced with 20 mg diethylnitrosamine/kg BW. Rats received daily by gastric gavage 65 mg irradiated β-glucan/kg BW. It was found that treatment of rats with diethylnitrosamine induced hepatic injury and caused significant increase in liver injury markers with a concomitant significant increase in both hepatic oxidative and inflammatory indices: alpha-fetoprotein, interferon gamma, and interleukin 6 in comparison with normal and irradiated β-glucan–treated groups. Western immunoblotting showed a significant increase in the signaling growth factors: extracellular signal–regulated kinase 1 and phosphoinositide 3-kinase proteins in a diethylnitrosamine-treated group while both preventive and therapeutic irradiated β-glucan treatments recorded significant improvement versus diethylnitrosamine group via the modulation of growth factors that encounters hepatic toxicity. The transcript levels of vascular endothelial growth factor A and inducible nitric oxide synthase genes were significantly higher in the diethylnitrosamine-treated group in comparison with controls. Preventive and therapeutic treatments with irradiated β-glucan demonstrated that the transcript level of these genes was significantly decreased which demonstrates the protective effect of β-glucan. Histological investigations revealed that diethylnitrosamine treatment affects the hepatic architecture throughout the significant severe appearance of inflammatory cell infiltration in the portal area and congestion in the portal vein in association with severe degeneration and dysplasia in hepatocytes all over hepatic parenchyma. The severity of hepatic architecture changes was significantly decreased with both β-glucan therapeutic and preventive treatments. In conclusion, irradiated β-glucan modulated signal growth factors, vascular endothelial growth factor A, extracellular signal–regulated kinase 1, and phosphatidylinositol-3-kinase, which contributed to experimental hepatocarcinogenesis.

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