Effect of advanced glycation end products on the expression of hypoxia-inducible factor-1α and vascular endothelial growth factor proteins in RF/6A cells

Zhang,Huiming; Tang,Luosheng; Chen,Siying; Yang,Yezhen; Chen,Mingjiazi; Luo,Jing

doi:10.3892/etm.2013.1015

May 2013 Volume 5 Issue 5

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May 2013 Volume 5 Issue 5

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Article

Effect of advanced glycation end products on the expression of hypoxia-inducible factor-1α and vascular endothelial growth factor proteins in RF/6A cells

Authors:
- Huiming Zhang
- Luosheng Tang
- Siying Chen
- Yezhen Yang
- Mingjiazi Chen
- Jing Luo
View Affiliations / Copyright

Affiliations: Department of Ophthalmology, The Second Xiangya Hospital, Xiangya School of Medicine, Central South University, Changsha, Hunan 410011, P.R. China
Pages: 1519-1522
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Published online on: March 15, 2013

https://doi.org/10.3892/etm.2013.1015
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Abstract

The aim of this study was to investigate the effect of advanced glycation end products (AGEs) on the expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) proteins in RF/6A cells cultured in vitro, and to investigate the association between the expression of HIF-1α and VEGF proteins. RF/6A cells were cultured in vitro and treated with AGEs and non-glycated albumin control at various concentrations (0, 50, 100, 200, 400 and 800 mg/l) for 24 h. The expression of the VEGF protein was detected by ELISA, and western blot analysis was used to determine the levels of HIF-1α protein. The expression of HIF-1α and VEGF proteins was significantly higher in the AGE group compared with the non-glycated control group (all P<0.05). With the increase in concentration of AGEs, the expression levels of HIF-1α and VEGF protein increased and reached a maximum at 200 mg/l AGE, then decreased at 400 and 800 mg/l. However this effect was not observed in the non‑glycated control groups. There was a positive correlation between the expression of HIF-1α and VEGF (P<0.05). AGEs induced the expression of HIF-1α and VEGF proteins in RF/6A cells in a concentration‑dependent manner. AGEs may upregulate the expression of VEGF protein by increasing the levels of HIF-1α protein, demonstrating the potential role of HIF-1α-targeted therapy in neovascularization.

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1.	Schleicher ED, Wagner E and Nerlich AG: Increased accumulation of the glycoxidation product N(epsilon)-carboxymethyl) lysine in human tissues in diabetes and aging. J Clin Invest. 99:457–468. 1997. View Article : Google Scholar : PubMed/NCBI
2.	Peppa M, Uribarri J and Vlassara H: Glucose, advanced glycation end products and diabetes complications: what is new and what works. Clin Diabetes. 21:186–187. 2003. View Article : Google Scholar
3.	Lu M, Kuroki M, Amano S, et al: Advanced glycation end products increase retinal vascular endothelial growth factor expression. J Clin Invest. 101:1219–1224. 1998. View Article : Google Scholar : PubMed/NCBI
4.	Simó R and Hernández C: Intravitreous anti-VEGF for diabetic retinopathy: hopes and fears for a new therapeutic strategy. Diabetologia. 51:1574–1580. 2008.PubMed/NCBI
5.	Bracken CP, Whitelaw ML and Peet DJ: The hypoxia-inducible factors: key transcriptional regulators of hypoxic responses. Cell Mol Life Sci. 60:1376–1393. 2003. View Article : Google Scholar : PubMed/NCBI
6.	Poulaki V, Joussen AM, Mitsiades N, et al: Insulin-like growth factor-I plays a pathogenetic role in diabetic retinopathy. Am J Pathol. 165:457–469. 2004. View Article : Google Scholar : PubMed/NCBI
7.	Makita Z, Vlassara H, Cerami A and Bucala R: Immunochemical detection of advanced glycosylation end products in vivo. J Biol Chem. 267:5133–5138. 1992.PubMed/NCBI
8.	Hammes HP, Alt A, Niwa T, et al: Differential accumulation of advanced glycation end products in the course of diabetic retinopathy. Diabetologia. 42:728–736. 1999. View Article : Google Scholar : PubMed/NCBI
9.	Aiello LP, Avery RL, Arrigg PG, et al: Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 331:1480–1487. 1994. View Article : Google Scholar : PubMed/NCBI
10.	Song E, Li TY, Xu Q, et al: Expression of vascular endothelial growth factor in retinopathy of diabetic rats. Int J Ophthalmol. 3:9–12. 2003.(In Chinese).
11.	Semenza GL: Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 3:721–732. 2003. View Article : Google Scholar
12.	Lin M, Chen Y, Jin J, et al: Ischaemia-induced retinal neovascularisation and diabetic retinopathy in mice with conditional knockout of hypoxia-inducible factor-1 in retinal Müller cells. Diabetologia. 54:1554–1566. 2011.PubMed/NCBI
13.	Wu HX and You ZP: Study progress of HIF-1 regulation mechanisms in diabetic retinopathy and neuropathy. Int J Ophthalmol. 9:102–105. 2009.(In Chinese).
14.	Okada K, Osaki M, Araki K, et al: Expression of hypoxia-inducible factor (HIF-1α), VEGF-C and VEGF-D in non-invasive and invasive breast ductal carcinomas. Anticancer Res. 25:3003–3009. 2005.
15.	Treins C, Giorgetti-Peraldi S, Murdaca J and Van Obberghen E: Regulation of vascular endothelial growth factor expression by advanced glycation end products. J Biol Chem. 276:43836–43841. 2001. View Article : Google Scholar : PubMed/NCBI
16.	Wang X, Wang G and Wang Y: Intravitreous vascular endothelial growth factor and hypoxia-inducible factor-1α in patients with proliferative diabetic retinopathy. Am J Ophthalmol. 148:883–889. 2009.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Effect of advanced glycation end products on the expression of hypoxia-inducible factor-1α and vascular endothelial growth factor proteins in RF/6A cells

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