Vascular endothelial growth factor upregulates pigment epithelium-derived factor expression via VEGFR-1 in human retinal pigment epithelial cells.
We previously demonstrated that differentiated retinal pigment epithelial (RPE) cells express high levels of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF), and a critical balance between VEGF and PEDF is important to prevent the development of choroidal neovascularization. We report here that VEGF secreted by RPE cells upregulates PEDF expression via VEGFR-1 in an autocrine manner. PEDF mRNA and protein expression was downregulated by neutralizing antibody against VEGF in differentiated human RPE cells. VEGFR-1 neutralization decreased PEDF mRNA and protein expression whereas anti-VEGFR-2 antibody had no effect. Addition of placenta growth factor (PlGF) restored PEDF expression in the presence of anti-VEGF antibody. These results demonstrate a regulatory interaction between angiogenesis stimulators and inhibitors to maintain homeostasis in normal human retina.
Ohno-Matsui
Kyoko
K
Department of Ophthalmology and Visual Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. k.ohno.oph@tmd.ac.jp
Yoshida
Takeshi
T
Uetama
Tomoko
T
Mochizuki
Manabu
M
Morita
Ikuo
I
D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000502:physiology*; D005136:Eye Proteins; D005246:Feedback; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D008222:Lymphokines / Q000037:antagonists & inhibitors / Q000502:physiology*; D018919:Neovascularization, Physiologic; D009414:Nerve Growth Factors; D010857:Pigment Epithelium of Eye / Q000098:blood supply / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000494:pharmacology; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015843:Serpins / Q000096:biosynthesis / Q000235:genetics*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors; D000099174:Pigment Epithelium-Derived Factor
D016228:Endothelial Growth Factors; D005136:Eye Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D009414:Nerve Growth Factors; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins; D011506:Proteins; D012333:RNA, Messenger; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D042442:Vascular Endothelial Growth Factors; D000099174:Pigment Epithelium-Derived Factor; C000608036:PGF protein, human