Hong Yanggang, Wang Deqi, Lin Yinfang, Yang Qianru, Wang Yi, Xie Yuanyuan, Shu Wanyi, Gao Sheng, Hua Chunyan
The Second School of Medicine, Wenzhou Medical University, Zhejiang Province 325035, China.
The First School of Medicine, Wenzhou Medical University, Zhejiang Province 325035, China.
Ecotoxicol Environ Saf. 2024 Dec;288:117352. doi: 10.1016/j.ecoenv.2024.117352. Epub 2024 Nov 16.
Bisphenol A (BPA), a chemical compound in plastics and resins, widely exist in people's production and life which have great potential to damage human and animal health. It has been proved that BPA could affect human immune function and promote the occurrence and development of autoimmune diseases (ADs). However, the mechanism and pathophysiology remain unknown. Therefore, this study aims to advance network toxicology strategies to efficiently investigate the putative toxicity and underlying molecular mechanisms of environmental pollutants, focusing on ADs induced by BPA exposure. Leveraging databases including ChEMBL, STITCH, SwissTargetPrediction, GeneCards, and OMIM, we identified potential targets associated with BPA exposure and ADs, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), Hashimoto's thyroiditis (HT), inflammatory bowel disease (IBD), and type 1 diabetes (T1D). Subsequent refinement using STRING and Cytoscape software highlighted core targets respectively, and Metascape was utilized for enrichment analysis. Gene expression data from the GEO database revealed the upregulation or downregulation of these targets across these ADs. Molecular docking performed with Autodock confirmed robust binding between BPA and core targets, notably PPARG, CTNNB1, ESR1, EGFR, SRC, and CCND1. These findings suggest that BPA exposure may serve as an environmental trigger in the development of autoimmunity, underscoring potential environmental risk factors for the onset of autoimmune conditions.
双酚A（BPA）是塑料和树脂中的一种化合物，广泛存在于人们的生产生活中，对人类和动物健康具有极大的潜在危害。已证实双酚A会影响人体免疫功能，并促进自身免疫性疾病（ADs）的发生发展。然而，其作用机制和病理生理学仍不清楚。因此，本研究旨在推进网络毒理学策略，以有效探究环境污染物的潜在毒性及潜在分子机制，重点关注双酚A暴露引发的自身免疫性疾病。利用包括ChEMBL、STITCH、SwissTargetPrediction、GeneCards和OMIM在内的数据库，我们确定了与双酚A暴露和自身免疫性疾病相关的潜在靶点，包括类风湿性关节炎（RA）、系统性红斑狼疮（SLE）、多发性硬化症（MS）、桥本甲状腺炎（HT）、炎症性肠病（IBD）和1型糖尿病（T1D）。随后使用STRING和Cytoscape软件分别对核心靶点进行了优化，并利用Metascape进行富集分析。来自GEO数据库的基因表达数据揭示了这些靶点在这些自身免疫性疾病中的上调或下调情况。使用Autodock进行的分子对接证实了双酚A与核心靶点之间有强大的结合，特别是过氧化物酶体增殖物激活受体γ（PPARG）、β-连环蛋白1（CTNNB1）、雌激素受体1（ESR1）、表皮生长因子受体（EGFR）、原癌基因酪氨酸蛋白激酶（SRC）和细胞周期蛋白D1（CCND1）。这些发现表明，双酚A暴露可能是自身免疫性疾病发展过程中的一个环境触发因素，凸显了自身免疫性疾病发病的潜在环境风险因素。
