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S. Sato, Y. Kawakami, S. Sakurai; Pigment Epithelium Derived Factor (PEDF) in Human Retinal Capillary Pericytes . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3884.
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Purpose: Pigment epithelium derived growth factor (PEDF) is a potent antiangiogenic factor and may play a key role in hypoxia-induced retinal angiopathy such as diabetic retinopathy or premature retinopathy. Since pericytes are known to regulate endothelial cell growth, we examined the expression of PEDF in human retinal pericytes and the effects of exogenous PEDF on pericyte and endothelial cell growth. Methods: Human retinal capillary pericytes were cultured in DMEM media supplemented with 10% FCS. Endothelial cells utilized in this study were human umbilical vein endothelial cells (HUVEC). The mRNA expression of PDGF and c-fos was examined by RT-PCR. Signal transduction assays were done with Western blot. Cell viability was evaluated by DNA synthesis (BrdU assay). Results: Pericytes expressed the high levels of PDGF mRNA while the expression of PDF in endothelial cells was almost undetectable. PEDF stimulates pericyte growth at both low (0.1-1.0 mg/ml) and high (50 mg/ml) doses. The stimulation by PEDF also activated MAPK and CREB and induced early response gene c-fos mRNA expression. In contrast, the effects of exogenous PEDF on endothelial cells were dose-dependent. PEDF increased cell growth at the low doses (0.1-1.0 mg/ml) while the viable cell number of endothelial cells was significantly decreased with high (50 mg/ml) dose of PEDF. More than 80% of cells treated with the high dose of PEDF were TUNEL positive, suggesting that endothelial cells undergo apoptosis under the high concentration of PEDF. Conclusions: Retinal capillary pericytes appear to be an important source of PEDF. In physiological condition, PEDF enhances pericyte viability and prevent endothelial cell growth. In the environment with low levels of PEDF, endothelial cell growth can be easily induced.
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