Kheitan Samira, Minuchehr Zarrin, Soheili Zahra-Soheila
Systems Biotechnology Department, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
Molecular Medicine Department, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
PLoS One. 2017 Jul 24;12(7):e0181667. doi: 10.1371/journal.pone.0181667. eCollection 2017.
Increasing evidence demonstrates that inflammation and endoplasmic reticulum (ER) stress is implicated in the development and progression of age-related macular degeneration (AMD), a multifactorial neurodegenerative disease. However the cross talk between these cellular mechanisms has not been clearly and fully understood. The present study investigates a possible intersection between ER stress and inflammation in AMD. In this study, we recruited two collections of involved protein markers to retrieve their interaction information from IMEx-curated databases, which are the most well- known protein-protein interaction collections, allowing us to design an intersection network for AMD that is unprecedented. In order to find expression activated subnetworks, we utilized AMD expression profiles in our network. In addition, we studied topological characteristics of the most expressed active subnetworks to identify the hubs. With regard to topological quantifications and expressional activity, we reported a list of the most pivotal hubs which are potentially applicable as probable therapeutic targets. Furthermore, we introduced MAPK signaling pathway as a significantly involved pathway in the association between ER stress and inflammation, leading to promising new directions in discovering AMD formation mechanisms and possible treatments.
越来越多的证据表明，炎症和内质网（ER）应激与年龄相关性黄斑变性（AMD）的发生和发展有关，AMD是一种多因素神经退行性疾病。然而，这些细胞机制之间的相互作用尚未得到清晰和充分的理解。本研究调查了AMD中ER应激与炎症之间可能的交叉点。在本研究中，我们收集了两组相关的蛋白质标志物，从IMEx整理的数据库中检索它们的相互作用信息，这些数据库是最著名的蛋白质-蛋白质相互作用集合，使我们能够设计出一个前所未有的AMD交叉网络。为了找到表达激活的子网，我们在网络中利用了AMD表达谱。此外，我们研究了表达最活跃的子网的拓扑特征以识别枢纽节点。关于拓扑量化和表达活性，我们报告了一系列最关键的枢纽节点，它们有可能作为潜在的治疗靶点。此外，我们引入丝裂原活化蛋白激酶（MAPK）信号通路作为ER应激与炎症关联中显著涉及的通路，为发现AMD形成机制和可能的治疗方法带来了有前景的新方向。
