Zhao Bojun, Cai Jun, Boulton Mike
Cell and Molecular Biology Unit, School of Optometry and Vision Sciences and Cardiff Institute of Tissue Engineering and Repair, Cardiff University, Cardiff CF10 3NB, UK.
Microvasc Res. 2004 Nov;68(3):239-46. doi: 10.1016/j.mvr.2004.07.004.
Placenta growth factor (PlGF) has been implicated in both physiological and pathological angiogenesis; however, little is known about what regulates its expression. In this study, retinal microvascular endothelial cells and pericytes were exposed to varying concentrations of VEGF and glucose and PlGF expression measured by RT-PCR and Western blotting. Both PlGF mRNA and protein were observed in unstimulated microvascular endothelial cells with only weak expression in pericytes. In endothelial cells, VEGF (100 ng/ml) and glucose (15 mM) induced an increase in expression of PlGF at both the mRNA and protein level while no effect was observed for pericytes. The increase in PlGF expression could be totally abolished by blocking VEGFR-2, and in the case of glucose by neutralising VEGF. VEGF-stimulated PlGF expression was largely inhibited by PD 98059, an inhibitor of mitogen-activated protein kinase (MAPK) and partially by GF 109203X, an inhibitor of protein kinase C (PKC), indicating that VEGF up-regulates PlGF expression via the MAPK signalling pathway and partially through PKC. Taken together, our findings suggest that VEGF orchestrates the contribution of PlGF in angiogenesis via more than one intracellular pathway and that hyperglycaemia, as occurs in diabetes, is an important regulator of PlGF expression via VEGF up-regulation.
胎盘生长因子（PlGF）与生理性和病理性血管生成均有关联；然而，对于调控其表达的因素却知之甚少。在本研究中，将视网膜微血管内皮细胞和周细胞暴露于不同浓度的血管内皮生长因子（VEGF）和葡萄糖中，并用逆转录聚合酶链反应（RT-PCR）和蛋白质印迹法检测PlGF的表达。在未受刺激的微血管内皮细胞中可观察到PlGF的信使核糖核酸（mRNA）和蛋白质，而在周细胞中仅有微弱表达。在内皮细胞中，VEGF（100纳克/毫升）和葡萄糖（15毫摩尔）可诱导PlGF在mRNA和蛋白质水平的表达增加，而周细胞未观察到影响。阻断血管内皮生长因子受体2（VEGFR-2）可完全消除PlGF表达的增加，而对于葡萄糖而言，通过中和VEGF可达到此效果。VEGF刺激的PlGF表达在很大程度上受到促分裂原活化蛋白激酶（MAPK）抑制剂PD 98059的抑制，部分受到蛋白激酶C（PKC）抑制剂GF 109203X的抑制，这表明VEGF通过MAPK信号通路并部分通过PKC上调PlGF的表达。综上所述，我们的研究结果表明，VEGF通过不止一条细胞内途径协调PlGF在血管生成中的作用，并且糖尿病中出现的高血糖症是通过上调VEGF而成为PlGF表达的重要调节因子。
