The regulation of vascular endothelial growth factors (VEGF-A, -C, and -D) expression in the retinal pigment epithelium

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• 作者：Yasuhiro Ikeda ; Yoshikazu Yonemitsu ; Mitsuho Onimaru ; Toshiaki Nakano ; Masanori Miyazaki ; Ri-ichiro Kohno ; Kazunori Nakagawa ; Akifumi Ueno ; Katsuo Sueishi and Tatsuro Ishibashi
• 关键词：retinal pigment epithelium ; hypoxia ; cell– ; cell adhesion ; cell– ; matrix adhesion
• 刊名：Experimental Eye Research
• 出版年：2006
• 出版时间：November 2006
• 年：2006
• 卷：83
• 期：5
• 页码：1031-1040
• 全文大小：567 K

文摘

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 Ca²⁺ 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.