Amano S, Yamagishi S, Inagaki Y, Okamoto T
Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
Int J Tissue React. 2003;25(2):51-5.
Platelet-derived growth factor-BB (PDGF-BB) is a potent mitogen and chemoattractant for microvascular endothelial cells and glial cells in the retina and is thus involved in the development of proliferative diabetic retinopathy. However, relatively little is known about the regulation of PDGF-B gene expression in retinal cells. In this study, we cloned partial complementary DNAs (cDNAs) encoding bovine PDGF-B and examined the effects of angiotensin II (Ang II), which is also implicated in the pathogenesis of diabetic retinopathy, on PDGF-B gene expression in bovine cultured retinal pericytes. Ang II was found to up-regulate PDGF-B messenger RNA (mRNA) levels in bovine retinal pericytes. Telmisartan, a newly developed Ang II type 1 receptor antagonist, or an antioxidant N-acetylcysteine significantly inhibited PDGF-B gene induction in Ang II-exposed pericytes. The present results suggest that Ang II-type 1 receptor interaction could stimulate PDGF-B gene expression in cultured retinal pericytes through intracellular reactive oxygen species generation and could thus be involved in the progression of diabetic retinopathy.
血小板衍生生长因子-BB(PDGF-BB)是一种对视网膜中的微血管内皮细胞和神经胶质细胞具有强大作用的促有丝分裂剂和趋化因子,因此参与了增殖性糖尿病视网膜病变的发展。然而,关于视网膜细胞中PDGF-B基因表达的调控,人们了解得相对较少。在本研究中,我们克隆了编码牛PDGF-B的部分互补DNA(cDNA),并研究了同样与糖尿病视网膜病变发病机制有关的血管紧张素II(Ang II)对牛视网膜周细胞中PDGF-B基因表达的影响。结果发现,Ang II可上调牛视网膜周细胞中PDGF-B信使核糖核酸(mRNA)水平。新型Ang II 1型受体拮抗剂替米沙坦或抗氧化剂N-乙酰半胱氨酸可显著抑制Ang II处理的周细胞中PDGF-B基因的诱导。目前的结果表明,Ang II 1型受体相互作用可能通过细胞内活性氧的产生刺激培养的视网膜周细胞中PDGF-B基因的表达,从而可能参与糖尿病视网膜病变的进展。