Effect of pigment epithelium derived factor on microvascular cells

Abstract

Objectives: Angiogenesis is a key process of tumor growth and metastasis. Recently, pigment epithelium derived factor (PEDF) is known as a potent antiangiogenic factor. We examined the expression of PEDF in human endothelial cells and pericytes as microvascular cells. Further we examined the effects of exogenous PEDF on endothelial cell and pericyte proliferation. Methods: Pericytes utilized in this study were human retinal capillary pericytes. Endothelial cells 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 proliferation was evaluated by DNA synthesis (BrdU assay). Results: Pericytes expressed the high levels of PDGF mRNA while the expression of PEDF in endothelial cells was almost undetectable. PEDF stimulates pericyte proliferation at both low (0.1–1.0 μg/mL) and high (50 μg/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 proliferation at the low doses (0.1–1.0 μg/ml) while cell proliferation was significantly decreased with high (50 μg/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. Conclusion: Pericyte is an important source of PEDF. In physiological condition, PEDF enhances pericyte viability and prevent endothelial cell proliferation. In the environment with low levels of PEDF, endothelial cell proliferation can be easily induced.