Huo Mengqi, Wang Zhixin, Wu Dongxue, Zhang Yanling, Qiao Yanjiang
Key Laboratory of Traditional Chinese Medicine Information Engineer of State Administration of Traditional Chinese Medicine; School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100102, China.
Int J Mol Sci. 2017 Jun 19;18(6):1298. doi: 10.3390/ijms18061298.
, known as Danshen, has attracted worldwide interest for its substantial effects on coronary heart disease (CHD). Danshensu (DSS) is one of the main active ingredients of Danshen on CHD. Although it has been proven to have a good clinical effect on CHD, the action mechanisms remain elusive. In the current study, a coexpression network-based approach was used to illustrate the beneficial properties of DSS in the context of CHD. By integrating the gene expression profile data and protein-protein interactions (PPIs) data, two coexpression protein interaction networks (CePIN) in a CHD state (CHD CePIN) and a non-CHD state (non-CHD CePIN) were generated. Then, shared nodes and unique nodes in CHD CePIN were attained by conducting a comparison between CHD CePIN and non-CHD CePIN. By calculating the topological parameters of each shared node and unique node in the networks, and comparing the differentially expressed genes, target proteins involved in disease regulation were attained. Then, Gene Ontology (GO) enrichment was utilized to identify biological processes associated to target proteins. Consequently, it turned out that the treatment of CHD with DSS may be partly attributed to the regulation of immunization and blood circulation. Also, it indicated that sodium/hydrogen exchanger 3 (SLC9A3), Prostaglandin G/H synthase 2 (PTGS2), Oxidized low-density lipoprotein receptor 1 (OLR1), and fibrinogen gamma chain (FGG) may be potential therapeutic targets for CHD. In summary, this study provided a novel coexpression protein interaction network approach to provide an explanation of the mechanisms of DSS on CHD and identify key proteins which maybe the potential therapeutic targets for CHD.
丹参因其对冠心病（CHD）的显著疗效而引起了全球关注。丹酚酸（DSS）是丹参治疗冠心病的主要活性成分之一。尽管已证明其对冠心病有良好的临床疗效，但其作用机制仍不清楚。在本研究中，采用基于共表达网络的方法来阐述丹酚酸在冠心病背景下的有益特性。通过整合基因表达谱数据和蛋白质-蛋白质相互作用（PPI）数据，生成了冠心病状态下的两个共表达蛋白质相互作用网络（CHD CePIN）和非冠心病状态下的（非CHD CePIN）。然后，通过比较CHD CePIN和非CHD CePIN获得CHD CePIN中的共享节点和独特节点。通过计算网络中每个共享节点和独特节点的拓扑参数，并比较差异表达基因，获得参与疾病调控的靶蛋白。然后，利用基因本体（GO）富集来识别与靶蛋白相关的生物学过程。结果表明，丹酚酸治疗冠心病可能部分归因于免疫调节和血液循环调节。此外，还表明钠/氢交换体3（SLC9A3）、前列腺素G/H合酶2（PTGS2）、氧化型低密度脂蛋白受体1（OLR1）和纤维蛋白原γ链（FGG）可能是冠心病的潜在治疗靶点。总之，本研究提供了一种新的共表达蛋白质相互作用网络方法，以解释丹酚酸对冠心病的作用机制，并识别可能是冠心病潜在治疗靶点的关键蛋白。
