The regulation of vascular endothelial growth factors (VEGF-A, -C, and -D) expression in the retinal pigment epithelium.
The vascular endothelial growth factor (VEGF) family plays an essential role in vascular development, angiogenesis and lymphangiogenesis. VEGF-A is a key regulator of endothelial cell functions and VEGF-C and VEGF-D are known to stimulate both angiogenesis and lymphangiogenesis. In a surgically removed subretinal vascular membrane of an age-related macular degeneration (AMD) patient, both VEGF-C and VEGF-D were confirmed, in addition to VEGF-A, to be markedly positive in the retinal pigment epithelium (RPE). There is no lymph vessel in ocular tissue, so it is possible that VEGF-C and VEGF-D expression in the RPE play some role in ocular angiogenesis, as well as VEGF-A. Next, we assessed the transition of VEGF-A, -C, and -D expression on several conditions, in human RPE. Hypoxia proverbially induced VEGF-A mRNA expression, meanwhile VEGF-C and VEGF-D mRNA expression was down-regulated. The Ca(2+) deprivation from culture medium strongly up-regulated VEGF-A and VEGF-D mRNA expression. Culture on plastic flasks precoated with poly-2-hydroxyethyl methacrylate up-regulated VEGF-D expression. Meanwhile, no significant change of VEGF-C mRNA expression was found in the blockade of cell-cell and/or cell-matrix adhesion. These findings suggest the possibility that VEGF-C and VEGF-D expression in RPE modify the ocular angiogenesis as angiogenic stimulators.
Ikeda
Yasuhiro
Y
Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. ymoc1@pathol1.med.kyushu-u.ac.jp
Yonemitsu
Yoshikazu
Y
Onimaru
Mitsuho
M
Nakano
Toshiaki
T
Miyazaki
Masanori
M
Kohno
Ri-ichiro
R
Nakagawa
Kazunori
K
Ueno
Akifumi
A
Sueishi
Katsuo
K
Ishibashi
Tatsuro
T
D000368:Aged; D002448:Cell Adhesion / Q000502:physiology; D002452:Cell Count; D002462:Cell Membrane / Q000235:genetics; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000502:physiology; D005136:Eye Proteins / Q000032:analysis*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D000860:Hypoxia / Q000235:genetics; D007150:Immunohistochemistry / Q000379:methods; D008268:Macular Degeneration / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000235:genetics; D010857:Pigment Epithelium of Eye / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D042582:Vascular Endothelial Growth Factor C / Q000032:analysis; D042643:Vascular Endothelial Growth Factor D / Q000032:analysis; D042442:Vascular Endothelial Growth Factors / Q000032:analysis*
D005136:Eye Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D042442:Vascular Endothelial Growth Factors