TGF-β1 prevents rat retinal insult induced by amyloid-β (1-42) oligomers
TGF-β1 prevents rat retinal insult induced by amyloid-β (1-42) oligomers
复制标题
DOI：
10.1016/j.ejphar.2016.02.002
复制
发表时间：
2016-09-15
影响因子：
5
通讯作者：
Bucolo, Claudio
中科院分区：
文献类型：
--
作者：
Fisichella, Vincenzo;Giurdanella, Giovanni;Bucolo, Claudio
目的：利用淀粉样蛋白β（A β）寡聚体建立模拟老年性黄斑变性（AMD）等病理状态的大鼠视网膜变性模型，并评价TGF-β 1的作用。使用Sprague-Dawley雄性大鼠。在存在或不存在重组人TGF-β 1（注射1 ng/μ l ITV）的情况下，玻璃体内（ITV）注射（10 μ M）人A β（1-42）寡聚体。48小时后，处死动物，取出眼睛并解剖。通过蛋白质印迹分析评估视网膜裂解物中的凋亡标志物Bax和Bcl-2。进行基因通路网络分析，以确定参与AMD的通路。用A β寡聚体处理诱导Bax蛋白水平的强烈增加（约4倍; p < 0.01）和Bcl-2蛋白水平的显著降低（约2倍; p < 0.05）。共注射TGF-β 1引发A β寡聚体诱导的Bax蛋白显著减少。生物信息学分析显示，Bcl-2和PI 3 K-Akt分别是AMD和阿尔茨海默病（AD）共同的丰富基因-通路网络中基因和通路的最连接节点。总之，这些数据表明，在大鼠中ITV注射A β（1-42）寡聚体诱导与大鼠视网膜中细胞凋亡相关的分子变化，突出了A β寡聚体在AMD中的潜在致病作用。生物信息学分析证实细胞凋亡途径参与了AMD的发病过程。此外，这些发现表明，人重组TGF-β 1可以预防A β寡聚体引起的视网膜损伤。(C)© 2016 Elsevier B. V.版权所有。
To set up a retinal degenerative model in rat that mimics pathologic conditions such as age-related macular degeneration (AMD) using amyloid-beta (A beta) oligomers, and assess the effect of TGF-beta 1. Sprague-Dawley male rats were used. Human A beta(1-42) oligomers were intravitreally (ITV) injected (10 mu M) in the presence or in the absence of recombinant human TGF-beta 1 (1 ng/mu l ITV injected). After 48 h, the animals were sacrificed and the eyes removed and dissected. The apoptotic markers Bax and Bcl-2 were assessed by western blot analysis in retina lysates. Gene-pathway network analysis was carried out in order to identify pathways involved in AMD. Treatment with A beta oligomers induced a strong increase in Bax protein level (about 4-fold; p < 0.01) and a significant reduction in Bcl-2 protein level (about 2-fold; p < 0.05). Co-injection of TGF-beta 1 triggered a significant reduction of Bax protein induced by A beta oligomers. Bioinformatic analysis revealed that Bcl-2 and PI3K-Akt are the most connected nodes, for genes and pathways respectively, in the enriched gene-pathway network common to AMD and Alzheimer disease (AD). Overall, these data indicate that ITV injection of A beta(1-42) oligomers in rat induces molecular changes associated with apoptosis in rat retina, highlighting a potential pathogenetic role of A beta oligomers in AMD. Bioinformatics analysis confirms that apoptosis pathways can take part in AMD. Furthermore, these findings suggest that human recombinant TGF-beta 1 can prevent retinal damage elicited by A beta oligomers. (C) 2016 Elsevier B.V. All rights reserved.