The First Clinical Medical College, Wenzhou Medical University, Wenzhou 325000, Zhejiang, P.R. China.
Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou 325000, Zhejiang, P.R. China.
Aging (Albany NY). 2021 May 18;13(10):14234-14257. doi: 10.18632/aging.203040.
Pulmonary arterial hypertension (PAH) is a devastating cardiovascular disease without a clear mechanism or drugs for treatment. Therefore, it is crucial to reveal the underlying molecular mechanism and identify potential drugs for PAH. In this study, we first integrated three human lung tissue datasets (GSE113439, GSE53408, GSE117261) from GEO. A total of 151 differentially expressed genes (DEGs) were screened, followed by KEGG and GO enrichment analyses and PPI network construction. Five hub genes (CSF3R, NT5E, ANGPT2, FGF7, and CXCL9) were identified by Cytoscape (Cytohubba). GSEA and GSVA were performed for each hub gene to uncover the potential mechanism. Moreover, to repurpose known and therapeutic drugs, the CMap database was retrieved, and nine candidate compounds (lypressin, ruxolitinib, triclabendazole, L-BSO, tiaprofenic acid, AT-9283, QL-X-138, huperzine-a, and L-741742) with a high level of confidence were obtained. Then ruxolitinib was selected to perform molecular docking simulations with ANGPT2, FGF7, NT5E, CSF3R, JAK1, JAK2, JAK3, TYK2. A certain concentration of ruxolitinib could inhibit the proliferation and migration of rat pulmonary artery smooth muscle cells (rPASMCs) . Together, these analyses principally identified CSF3R, NT5E, ANGPT2, FGF7 and CXCL9 as candidate biomarkers of PAH, and ruxolitinib might exert promising therapeutic action for PAH.
肺动脉高压（PAH）是一种破坏性的心血管疾病，其发病机制尚不清楚，也没有明确的治疗药物。因此，揭示其潜在的分子机制并寻找潜在的治疗药物至关重要。在本研究中，我们首先整合了 GEO 数据库中的三个人类肺组织数据集（GSE113439、GSE53408、GSE117261）。共筛选出 151 个差异表达基因（DEGs），然后进行了 KEGG 和 GO 富集分析以及 PPI 网络构建。通过 Cytoscape（Cytohubba）鉴定了五个枢纽基因（CSF3R、NT5E、ANGPT2、FGF7 和 CXCL9）。对每个枢纽基因进行了 GSEA 和 GSVA 分析，以揭示潜在的机制。此外，为了重新利用已知的和治疗性药物，检索了 CMap 数据库，获得了 9 种候选化合物（加压素、鲁索利替尼、三氯苯达唑、L-BSO、替普瑞酸、AT-9283、QL-X-138、石杉碱甲和 L-741742），置信度较高。然后选择鲁索利替尼与 ANGPT2、FGF7、NT5E、CSF3R、JAK1、JAK2、JAK3 和 TYK2 进行分子对接模拟。一定浓度的鲁索利替尼可以抑制大鼠肺动脉平滑肌细胞（rPASMCs）的增殖和迁移。综上所述，这些分析主要确定 CSF3R、NT5E、ANGPT2、FGF7 和 CXCL9 为 PAH 的候选生物标志物，鲁索利替尼可能对 PAH 具有潜在的治疗作用。
