Ozaki S, Johnson L V, Mullins R F, Hageman G S, Anderson D H
Neuroscience Research Institute, University of California, Santa Barbara, California, 93106, USA.
Biochem Biophys Res Commun. 1999 May 19;258(3):524-9. doi: 10.1006/bbrc.1999.0672.
Vitronectin (Vn), a multifunctional plasma protein synthesized primarily in the liver, is often present as a component of the extracellular plaques and deposits that accompany various age-related human diseases. Recently, we reported that Vn is also a prominent molecular constituent of drusen, the extracellular deposits associated with age-related macular degeneration (AMD) (1). The cellular source(s) of the Vn in drusen, as well as in these other plaques and deposits, remains uncertain. In this study, we used real-time quantitative RT-PCR to measure the relative levels of Vn mRNA in the cells and tissues that lie in close proximity to drusen. The results confirm that the human liver is an abundant source of Vn mRNA. Levels of Vn mRNA in kidney, lung, and fetal or adult brain are <3% of those in liver. Remarkably, mean Vn mRNA levels in the neural retina significantly exceed those in brain and represent close to 40% of the Vn mRNA value measured in human liver. Substantial levels of Vn mRNA are also present in the adjacent retinal pigment epithelium (RPE). These results identify the neural retina, for the first time, as an abundant source of Vn mRNA. They also suggest that both the neural retina and RPE are potent biosynthetic sources of Vn in humans, and potentially significant local contributors to the Vn that accumulates in drusen.
玻连蛋白(Vn)是一种主要在肝脏中合成的多功能血浆蛋白,常作为细胞外斑块和沉积物的成分存在,这些斑块和沉积物与多种人类年龄相关疾病相伴。最近,我们报道Vn也是玻璃膜疣的主要分子成分,玻璃膜疣是与年龄相关性黄斑变性(AMD)相关的细胞外沉积物(1)。玻璃膜疣以及其他这些斑块和沉积物中Vn的细胞来源仍不确定。在本研究中,我们使用实时定量逆转录聚合酶链反应(RT-PCR)来测量紧邻玻璃膜疣的细胞和组织中Vn mRNA的相对水平。结果证实人类肝脏是Vn mRNA的丰富来源。肾脏、肺以及胎儿或成人脑中的Vn mRNA水平低于肝脏中的3%。值得注意的是,神经视网膜中的平均Vn mRNA水平显著超过脑中的水平,接近人类肝脏中测量的Vn mRNA值的40%。相邻的视网膜色素上皮(RPE)中也存在大量的Vn mRNA。这些结果首次确定神经视网膜是Vn mRNA的丰富来源。它们还表明神经视网膜和RPE都是人类Vn的强大生物合成来源,并且可能是玻璃膜疣中积累的Vn的重要局部贡献者。