通过生物信息学分析和分子对接研究基底膜相关椎间盘退变的潜在分子靶点和药物。
Potential molecular targets and drugs for basement membranes-related intervertebral disk degeneration through bioinformatics analysis and molecular docking.
机构信息
The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P.R. China.
Department of Spinal Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P.R. China.
出版信息
BMC Musculoskelet Disord. 2023 Oct 2;24(1):772. doi: 10.1186/s12891-023-06891-z.
BACKGROUND
Through bioinformatics analysis to identify the hub genes of Intervertebral disc degeneration (IVDD) associated with basement membranes (BMs) and find out the potential molecular targets and drugs for BMs-related annulus fibrosus (AF) degeneration based on bioinformatic analysis and molecular approach.
METHODS
Intervertebral disc degeneration (IVDD) related targets were obtained from GeneCards, DisGenet and OMIM databases. BMs related genes were obtained from Basement membraneBASE database. The intersection targets were identified and subjected to protein-to-protein interaction (PPI) construction via STRING. Hub genes were identified and conducted Gene ontology (GO) and pathway enrichment analysis through MCODE and Clue GO in Cytospace respectively. DSigDB database was retrieved to predict therapeutic drugs and molecular docking was performed through PyMOL, AutoDock 1.5.6 to verify the binding energy between the drug and the different expressed hub genes. Finally, GSE70362 from GEO database was obtained to verify the different expression and correlation of each hub gene for AF degeneration.
RESULTS
We identified 41 intersection genes between 3 disease targets databases and Basement membraneBASE database. PPI network revealed 25 hub genes and they were mainly enriched in GO terms relating to glycosaminoglycan catabolic process, the TGF-β signaling pathway. 4 core targets were found to be significant via comparison of microarray samples and they showed strong correlation. The molecular docking results showed that the core targets have strong binding energy with predicting drugs including chitosamine and retinoic acid.
CONCLUSIONS
In this study, we identified hub genes, pathways, potential targets, and drugs for treatment in BMs-related AF degeneration and IVDD.
背景
通过生物信息学分析，鉴定与基底膜（BMs）相关的椎间盘退变（IVDD）的枢纽基因，并基于生物信息学分析和分子方法，找出潜在的与 BMs 相关的纤维环（AF）退变的分子靶点和药物。
方法
从 GeneCards、DisGenet 和 OMIM 数据库中获取与椎间盘退变（IVDD）相关的靶点。从 Basement membraneBASE 数据库中获取与基底膜相关的基因。通过 STRING 构建蛋白质-蛋白质相互作用（PPI）网络，鉴定交集靶点。通过 Cytospace 中的 MCODE 和 ClueGO 进行基因本体论（GO）和通路富集分析，鉴定枢纽基因。通过 DSigDB 数据库预测治疗药物，并通过 PyMOL、AutoDock 1.5.6 进行分子对接，验证药物与不同表达的枢纽基因之间的结合能。最后，从 GEO 数据库中获取 GSE70362，以验证每个枢纽基因在 AF 退变中的差异表达和相关性。
结果
我们在 3 个疾病靶点数据库和 Basement membraneBASE 数据库之间鉴定了 41 个交集基因。PPI 网络揭示了 25 个枢纽基因，它们主要富集在与糖胺聚糖分解代谢、TGF-β 信号通路相关的 GO 术语中。通过比较微阵列样本，发现 4 个核心靶点具有显著性，它们之间具有很强的相关性。分子对接结果表明，核心靶点与预测药物包括壳聚糖和维甲酸具有很强的结合能。
结论
本研究鉴定了与 BMs 相关的 AF 退变和 IVDD 的枢纽基因、通路、潜在靶点和治疗药物。
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