Longeras Richard, Farjo Krysten, Ihnat Michael, Ma Jian-Xing
Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma, OK 73104, USA.
Exp Diabetes Res. 2012;2012:518426. doi: 10.1155/2012/518426. Epub 2011 Jun 28.
Proliferative diabetic retinopathy is characterized by pathological retinal neovascularization, mediated by both angiogenesis (involving mature endothelial cells) and vasculogenesis (involving bone marrow-derived circulating endothelial progenitor cells (EPCs)). Pigment epithelium-derived factor (PEDF) contains an N-terminal 34-amino acid peptide (PEDF-34) that has antiangiogenic properties. Herein, we present a novel finding that PEDF-34 also possesses antivasculogenic activity. In the oxygen-induced retinopathy (OIR) model using transgenic mice that have Tie2 promoter-driven GFP expression, we quantified Tie2GFP(+) cells in bone marrow and peripheral blood by fluorescence-activated cell sorting (FACS). OIR significantly increased the number of circulating Tie2-GFP(+) at P16, correlating with the peak progression of neovascularization. Daily intraperitoneal injections of PEDF-34 into OIR mice decreased the number of Tie2-GFP(+) cells in the circulation at P16 by 65% but did not affect the number of Tie2-GFP(+) cells in the bone marrow. These studies suggest that PEDF-34 attenuates EPC mobilization from the bone marrow into the blood circulation during retinal neovascularization.
增殖性糖尿病视网膜病变的特征是病理性视网膜新生血管形成，这一过程由血管生成（涉及成熟内皮细胞）和血管发生（涉及骨髓来源的循环内皮祖细胞（EPCs））介导。色素上皮衍生因子（PEDF）包含一个具有抗血管生成特性的N端34个氨基酸的肽段（PEDF-34）。在此，我们提出一个新发现，即PEDF-34也具有抗血管发生活性。在使用具有Tie2启动子驱动的绿色荧光蛋白（GFP）表达的转基因小鼠的氧诱导视网膜病变（OIR）模型中，我们通过荧光激活细胞分选（FACS）对骨髓和外周血中的Tie2GFP(+)细胞进行了定量。OIR在P16时显著增加了循环中Tie2-GFP(+)细胞的数量，这与新生血管形成的峰值进展相关。每天给OIR小鼠腹腔注射PEDF-34可使P16时循环中Tie2-GFP(+)细胞的数量减少65%，但不影响骨髓中Tie2-GFP(+)细胞的数量。这些研究表明，PEDF-34在视网膜新生血管形成过程中可减弱EPC从骨髓向血液循环的动员。
