全反式维甲酸通过网络药理学和分子对接与类风湿关节炎相关靶基因结合的分子基础。

The molecular basis of all-trans retinoic acid binding to the target genes involved in rheumatoid arthritis through network pharmacology and molecular docking.

作者信息

Zheng Xi, Ke Xin, Gao Jie, Zheng Zhaohui, Zhu Ping

机构信息

Department of Clinical Immunology of Xijing Hospital, Department of Cell Biology of National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, 710032, China.

出版信息

Clin Rheumatol. 2025 May 17. doi: 10.1007/s10067-025-07482-0.

DOI:10.1007/s10067-025-07482-0

PMID:40379851

Abstract

OBJECTIVE

All-trans retinoic acid (ATRA), a natural derivative of Vitamin A, plays a crucial role in cellular proliferation, differentiation, and metabolic functions. It has been reported to possess significant antioxidant and anti-inflammatory properties. However, a comprehensive investigation into its potential mechanisms within the framework of rheumatoid arthritis (RA) has yet to be adequately addressed.

METHODS

This study aimed to identify potential targets of ATRA by employing databases such as DrugBank and SwissTargetPrediction. Furthermore, disease-associated genes relevant to rheumatoid arthritis were sourced from DisGeNET and GeneCards. Analyses of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were conducted. Drug-target-pathway networks were developed, and significant hub genes were identified. In addition, molecular docking studies were performed to assess the binding affinity of ATRA.

RESULTS

The results indicated that ATRA engages with 127 identified target genes, of which 85 are linked to rheumatoid arthritis (RA). Analyses employing Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and network approaches suggested that these targets participate in inflammatory pathways and metabolic processes pertinent to RA. Additionally, molecular docking studies revealed a significant binding affinity between ATRA and the proteins CYP1A1 and CYP2B6.

CONCLUSION

ATRA is anticipated to engage with various proteins and pathways associated with rheumatoid arthritis, suggesting its potential utility in the clinical management of this disorder. Key Points • All-trans retinoic acid (ATRA) has been shown to interact with 85 specific genes in patients with RA, among which 10 key hub genes have been identified. • Molecular docking studies indicate that ATRA exhibits the lowest binding affinity with the genes CYP1 A1 and CYP2B6.

摘要

目的

全反式维甲酸（ATRA）是维生素A的天然衍生物，在细胞增殖、分化和代谢功能中起关键作用。据报道，它具有显著的抗氧化和抗炎特性。然而，在类风湿性关节炎（RA）框架内对其潜在机制的全面研究尚未得到充分解决。

方法

本研究旨在通过使用DrugBank和SwissTargetPrediction等数据库来确定ATRA的潜在靶点。此外，与类风湿性关节炎相关的疾病相关基因来自DisGeNET和GeneCards。进行了基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析。构建了药物-靶点-通路网络，并确定了重要的枢纽基因。此外，进行了分子对接研究以评估ATRA的结合亲和力。

结果

结果表明，ATRA与127个已鉴定的靶基因相互作用，其中85个与类风湿性关节炎（RA）相关。采用基因本体论（GO）、京都基因与基因组百科全书（KEGG）和网络方法的分析表明，这些靶点参与了与RA相关的炎症通路和代谢过程。此外，分子对接研究揭示了ATRA与CYP1A1和CYP2B6蛋白之间具有显著的结合亲和力。