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

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World Journal of Gastroenterology 2012年第15期18卷 1781-1788页

作者： junichi takino Shoichi Yamagishi Masayoshi Takeuchi Department of Biochemistry Faculty of Pharmaceutical SciencesHiroshima International UniversityHiroshima 737-0112Japan Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications Kurume University School of MedicineKurume 830-0011Japan Department of Advanced Medicine Medical Research InstituteKanazawa Medical UniversityIshikawa 920-0293Japan

AIM:To investigate the effect of glyceraldehyde-derived advanced glycation end-products(Glycer-AGEs) on hepatocellular carcinoma(HCC)***:Two HCC cell lines(Hep3B and HepG2 cells)and human umbilical vein endothelial cells(HUVEC)were *** viability was determined using the WST-8 *** blotting,enzyme linked immunosorbent assay,and real-time reverse transcriptionpolymerase chain reactions were used to detect protein and *** was evaluated by assessing the proliferation,migration,and tube formation of ***:The receptor for AGEs(RAGE)protein was detected in Hep3B and HepG2 ***2 cells werenot affected by the addition of *** markedly increased vascular endothelial growth factor(VEGF)mRNA and protein expression,which is one of the most potent angiogenic *** 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.

关键词： Advanced glycation end-products Angiogenesis Glyceraldehyde Hepatocellular carcinoma Nonalcoholic steatohepatitis

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