Brief Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Apr 21, 2012; 18(15): 1781-1788
Published online Apr 21, 2012. doi: 10.3748/wjg.v18.i15.1781
Glycer-AGEs-RAGE signaling enhances the angiogenic potential of hepatocellular carcinoma by upregulating VEGF expression
Junichi Takino, Shoichi Yamagishi, Masayoshi Takeuchi
Junichi Takino, Department of Biochemistry, Faculty of Pharmaceutical Sciences, Hiroshima International University, Hiroshima 737-0112, Japan
Shoichi Yamagishi, Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume 830-0011, Japan
Masayoshi Takeuchi, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Ishikawa 920-0293, Japan
Author contributions: Takino J performed the study and wrote the paper; Takeuchi M designed the study and reviewed the paper; and Yamagishi S contributed experimental reagents.
Supported by Grants from the Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), No. 22300264
Correspondence to: Masayoshi Takeuchi, PhD, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Kahoku, Ishikawa 920-0293, Japan. takeuchi@kanazawa-med.ac.jp
Telephone: +81-76-2862211 Fax: +81-76-2863652
Received: December 9, 2011
Revised: February 7, 2012
Accepted: February 16, 2012
Published online: April 21, 2012
Abstract

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 transcription-polymerase 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 were not affected by the addition of Glycer-AGEs. Glycer-AGEs 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-AGEs-treated 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.

Keywords: Advanced glycation end-products; Angiogenesis; Glyceraldehyde; Hepatocellular carcinoma; Nonalcoholic steatohepatitis