title: Resveratrol suppresses vascular endothelial growth factor secretion via inhibition of CXC-chemokine receptor 4 expression in ARPE-19 cells.
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.
authors: Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 660‑751, Republic of Korea.
authors: Hyemin
authors: H
authors: Seong
authors: Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 660‑751, Republic of Korea.
authors: Jinhyun
authors: J
authors: Ryu
authors: Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 660‑751, Republic of Korea.
authors: Joo Yeon
authors: JY
authors: Jeong
authors: Department of Ophthalmology, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 660‑751, Republic of Korea.
authors: In Young
authors: IY
authors: Chung
authors: Department of Ophthalmology, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 660‑751, Republic of Korea.
authors: Yong-Seop
authors: YS
authors: Han
authors: Department of Neurosurgery, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 660‑751, Republic of Korea.
authors: Soo Hyun
authors: SH
authors: Hwang
authors: Department of Ophthalmology, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 660‑751, Republic of Korea.
authors: Jong Moon
authors: JM
authors: Park
authors: Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 660‑751, Republic of Korea.
authors: Sang Soo
authors: SS
authors: Kang
authors: Department of Ophthalmology, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 660‑751, Republic of Korea.
authors: Seong Wook
authors: SW
authors: Seo
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000096:biosynthesis* / Q000235:genetics; D003035:Cobalt / Q000633:toxicity; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D016328:NF-kappa B / Q000235:genetics; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics; D000077185:Resveratrol; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000008:administration & dosage*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016328:NF-kappa B; D019718:Receptors, CXCR4; D013267:Stilbenes; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003035:Cobalt; C018021:cobaltous chloride; D000077185:Resveratrol