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

作　　者：Junichi Takino Shoichi Yamagishi Masayoshi Takeuchi 

机构地区：[1]Department of Biochemistry,Faculty of Pharmaceutical Sciences,Hiroshima International University,Hiroshima 737-0112,Japan [2]Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications,Kurume University School of Medicine,Kurume 830-0011,Japan [3]Department of Advanced Medicine,Medical Research Institute,Kanazawa Medical University,Ishikawa 920-0293,Japan

出　　处：《World Journal of Gastroenterology》2012年第15期1781-1788,共8页世界胃肠病学杂志（英文版）

基　　金：Supported by Grants from the Japan Society for the Promotion of Science,Grant-in-Aid for Scientific Research(B),No.22300264

摘　　要：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(P<0.01).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(P<0.01).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(P<0.01).CONCLUSION:These results suggest that Glycer-AGEs-RAGE signaling enhances the angiogenic potential of HCC cells by upregulating VEGF expression.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.

关 键 词：Advanced glycation end-products ANGIOGENESIS GLYCERALDEHYDE Hepatocellular carcinoma Nonalcoholic steatohepatitis 

分 类 号：R735.7[医药卫生—肿瘤]