College of Life Science, Jiangxi Science & Technology Normal University, Nanchang, Jiangxi, China.
BMC Complement Med Ther. 2023 Oct 5;23(1):352. doi: 10.1186/s12906-023-04171-w.
Swertiamarin is the main hepatoprotective component of Swertiapatens and has anti-inflammatory and antioxidation effects. Our previous study showed that it was a potent inhibitor of idiopathic pulmonary fibrosis (IPF) and can regulate the expressions of α-smooth muscle actin (α-SMA) and epithelial cadherin (E-cadherin), two markers of the TGF-β/Smad (transforming growth factor beta/suppressor of mothers against decapentaplegic family) signaling pathway. But its targets still need to be investigated. The main purpose of this study is to identify the targets of swertiamarin.
GEO2R was used to analyze the differentially expressed genes (DEGs) of GSE10667, GSE110147, and GSE71351 datasets from the Gene Expression Omnibus (GEO) database. The DEGs were then enriched with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis for their biological functions and annotated terms. The protein-protein interaction (PPI) network was constructed to identify hub genes. The identified hub genes were predicted for their bindings to swertiamarin by molecular docking (MD) and validated by experiments.
76 upregulated and 27 downregulated DEGs were screened out. The DEGs were enriched in the biological function of cellular component (CC) and 7 cancer-related signaling pathways. Three hub genes, i.e., LOX (lysyl oxidase), COL5A2 (collagen type V alpha 2 chain), and CTGF (connective tissue growth factor) were selected, virtually tested for the interactions with swertiamarin by MD, and validated by in vitro experiments.
LOX, COL5A2, and CTGF were identified as the targets of swertiamarin on IPF.
獐牙菜苦苷是獐牙菜属的主要肝保护成分，具有抗炎和抗氧化作用。我们之前的研究表明，它是特发性肺纤维化（IPF）的有效抑制剂，可调节转化生长因子-β/信号转导与转录激活因子（TGF-β/Smad）信号通路的两个标志物α-平滑肌肌动蛋白（α-SMA）和上皮钙黏蛋白（E-cadherin）的表达。但其靶点仍需进一步研究。本研究的主要目的是鉴定獐牙菜苦苷的靶点。
使用 GEO2R 分析来自基因表达综合数据库（GEO）的 GSE10667、GSE110147 和 GSE71351 数据集的差异表达基因（DEGs）。然后，通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析对 DEGs 进行富集，以了解其生物学功能和注释术语。构建蛋白质-蛋白质相互作用（PPI）网络以识别枢纽基因。通过分子对接（MD）预测鉴定的枢纽基因与獐牙菜苦苷的结合，并通过实验验证。
筛选出 76 个上调和 27 个下调的 DEGs。DEGs 富集在细胞成分（CC）的生物学功能和 7 种癌症相关信号通路中。选择了 3 个枢纽基因，即 LOX（赖氨酰氧化酶）、COL5A2（胶原 V 型α2 链）和 CTGF（结缔组织生长因子），通过 MD 虚拟测试它们与獐牙菜苦苷的相互作用，并通过体外实验验证。
LOX、COL5A2 和 CTGF 被确定为獐牙菜苦苷治疗 IPF 的靶点。
