Resveratrol suppresses vascular endothelial growth factor secretion via inhibition of CXC-chemokine receptor 4 expression in ARPE-19 cells

Seong,Hyemin; Ryu,Jinhyun; Jeong,Joo  Yeon; Chung,In Young; Han,Yong‑Seop; Hwang,Soo  Hyun; Park,Jong  Moon; Kang,Sang  Soo; Seo,Seong  Wook

doi:10.3892/mmr.2015.3518

Resveratrol suppresses vascular endothelial growth factor secretion via inhibition of CXC-chemokine receptor 4 expression in ARPE-19 cells

Authors:
- Hyemin Seong
- Jinhyun Ryu
- Joo Yeon Jeong
- In Young Chung
- Yong‑Seop Han
- Soo Hyun Hwang
- Jong Moon Park
- Sang Soo Kang
- Seong Wook Seo
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Affiliations: Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 660‑751, Republic of Korea, Department of Ophthalmology, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 660‑751, Republic of Korea, Department of Neurosurgery, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 660‑751, Republic of Korea
Published online on: March 20, 2015 https://doi.org/10.3892/mmr.2015.3518
Pages: 1479-1484

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Abstract

The present study characterizes the effects of resveratrol (Res) on vascular endothelial growth factor (VEGF) secretion in retinal pigment epithelial (RPE) cells. ARPE‑19 cells were treated with CoCl2, a hypoxia mimetic agent. CoCl2 treatment increased protein levels of hypoxia inducible factor‑1α (HIF‑1α) and CXC‑chemokine receptor 4 (CXCR4), and secretion of VEGF. To confirm the effects of Res on VEGF secretion, the human umbilical vein endothelial cell tube formation assay was performed with conditioned medium from Res‑treated ARPE‑19 cells. The well‑known antioxidant Res effectively blocked these effects and reduced phosphorylation of nuclear factor (NF)‑κB, an upstream activator of CXCR4. Furthermore, Res also suppressed VEGF secretion induced by SDF‑1, a ligand of CXCR4. Conditioned medium from Res‑treated ARPE‑19 cells clearly suppressed tube formation compared with hypoxia‑treated conditioned medium. The results demonstrated that Res inhibited the hypoxia mimetic CoCl2‑induced expression of VEGF in ARPE‑19 cells. Res suppressed CXCR4 expression through decreased phosphorylation of NF‑κB, resulting in downregulation of VEGF secretion.

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