Glycer-AGEs-RAGE signaling enhances the angiogenic potential of hepatocellular carcinoma by upregulating VEGF expression

• Published in: World journal of gastroenterology : WJG Vol. 18; no. 15; pp. 1781 - 1788
• Main Authors: Takino, Junichi, Yamagishi, Shoichi, Takeuchi, Masayoshi
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Co., Limited 21-04-2012
• Subjects: Brief; Carcinoma, Hepatocellular - blood supply; Carcinoma, Hepatocellular - pathology; Cell Movement; Glycation End Products, Advanced - physiology; Glyceraldehyde; Hep G2 Cells; HepG2细胞; Humans; Liver Neoplasms - blood supply; Liver Neoplasms - pathology; mRNA表达水平; Neovascularization, Pathologic - etiology; RAGE; Receptor for Advanced Glycation End Products; Receptors, Immunologic - physiology; Signal Transduction - physiology; Up-Regulation; Vascular Endothelial Growth Factor A - physiology; VEGF; 信号增强; 肝癌细胞; 血管内皮生长因子; 血管生成因子; Angiogenesis; Hepatocellular carcinoma; Advanced glycation end-products; Nonalcoholic steatohepatitis; Glyceraldehyde
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v18.i15.1781

AIM：To investigate the effect of glyceraldehyde-derived advanced glycation end-products（Glycer-AGEs） on hepatocellular carcinoma（HCC）cells.METHODS：Two HCC cell lines（Hep3B and HepG2 cells）and human umbilical vein endothelial cells（HUVEC）were used.Cell viability was determined using the WST-8 assay.Western blotting,enzyme linked immunosorbent assay,and real-time reverse transcriptionpolymerase chain reactions were used to detect protein and mRNA.Angiogenesis was evaluated by assessing the proliferation,migration,and tube formation of HUVEC.RESULTS：The receptor for AGEs（RAGE）protein was detected in Hep3B and HepG2 cells.HepG2 cells werenot affected by the addition of Glycer-AGEs.GlycerAGEs markedly increased vascular endothelial growth factor（VEGF）mRNA and protein expression,which is one of the most potent angiogenic factors.Compared with the control unglycated bovine serum albumin（BSA） treatment,VEGF mRNA expression levels induced by the Glycer-AGEs treatment were 1.00±0.10 vs 1.92 ±0.09（P0.01）.Similarly,protein expression levels induced by the Glycer-AGEs treatment were 1.63±0.04 ng/mL vs 2.28±0.17 ng/mL for the 24 h treatment and 3.36±0.10 ng/mL vs 4.79±0.31 ng/mL for the 48 h treatment,respectively（P0.01）.Furthermore,compared with the effect of the control unglycated BSA-treated conditioned medium,the Glycer-AGEstreated conditioned medium significantly increased the proliferation,migration,and tube formation of HUVEC,with values of 122.4%±9.0%vs 144.5%±11.3%for cell viability,4.29±1.53 vs 6.78±1.84 for migration indices,and 71.0±7.5 vs 112.4±8.0 for the number of branching points,respectively（P0.01）.CONCLUSION：These results suggest that Glycer-AGEs-RAGE signaling enhances the angiogenic potential of HCC cells by upregulating VEGF expression.