Biotechnology Division, Institute of Himalayan Bioresource Technology, Council of Scientific and Industrial Research (CSIR-IHBT), Palampur, India.
OMICS. 2013 Jun;17(6):302-17. doi: 10.1089/omi.2012.0115.
Network biology-inspired approaches could be used effectively in probing regulatory processes by which small molecules intervene with disease mechanisms. The present study aims at identification of key targets of type 2 diabetes mellitus (T2DM) by network analysis of the underlying protein interactome, and probing for mechanisms by which phloridzin could be critical at altering the disease phenotype. Towards this goal, we constructed a protein-protein interaction network associated with T2DM, starting from candidate genes and systems-level interactions data available. The relevance of the network constructed was verified with the help of gene ontology, node deletion, and biological essentiality studies. Using a network analysis method, MAPK1, EP300, and SMAD2 were identified as the most central proteins of potential therapeutic value. Phloridzin, a known antidiabetic agent, potentially interacts with proteins central to T2DM mechanisms. The structural understanding of interaction of phloridzin with these proteins of relevance to T2DM could provide better insight into its regulatory mechanisms and help in developing better therapeutic agents. The molecular docking results suggest that phloridzin is potentially involved in making critical interactions with MAPK1. These results could further be validated by experimental studies and could be used to design therapeutic agents for T2DM intervention.
受网络生物学启发的方法可以有效地用于探测小分子通过何种调控过程干预疾病机制。本研究旨在通过对潜在蛋白质互作网络进行网络分析，鉴定 2 型糖尿病（T2DM）的关键靶点，并探究根皮苷改变疾病表型的作用机制。为此，我们从现有候选基因和系统水平互作数据出发，构建了一个与 T2DM 相关的蛋白质-蛋白质互作网络。借助基因本体论、节点删除和生物学重要性研究，验证了所构建网络的相关性。通过网络分析方法，确定 MAPK1、EP300 和 SMAD2 为具有潜在治疗价值的最核心蛋白。根皮苷是一种已知的抗糖尿病药物，可能与 T2DM 机制相关的核心蛋白相互作用。对根皮苷与这些与 T2DM 相关的重要蛋白相互作用的结构理解，可为其调控机制提供更深入的认识，并有助于开发更好的治疗药物。分子对接结果表明，根皮苷可能与 MAPK1 发生关键相互作用。这些结果可以通过实验研究进一步验证，并可用于设计用于 T2DM 干预的治疗药物。
