网络毒理学揭示了草甘膦在肾损伤和癌症中的作用机制。

Network toxicology reveals glyphosate mechanisms in kidney injury and cancer​​.

作者信息

Dong Yiling, Zhu Jufan

机构信息

General Practice Department, Tongxiang Wutong Street Community Health Service Center, Jiaxing, 314500, Zhejiang, China.

Institute of Organoid Technology, Kunming Medical University, Kunming, 650500, Yunnan, China.

出版信息

Sci Rep. 2025 Aug 24;15(1):31132. doi: 10.1038/s41598-025-17067-1.

Abstract

Molecular mechanisms underlying glyphosate-induced nephrotoxicity and carcinogenicity were investigated through integrated network toxicology, molecular docking, and dynamics simulations. Screening identified 47 potential glyphosate targets; intersection analysis yielded 20 kidney injury and 31 kidney cancer shared targets. Protein-protein interaction networks highlighted matrix metalloproteinases (MMP9, MMP2, MMP8, MMP3) and PLG as topological hubs. Pathway enrichment revealed significant alterations in extracellular matrix reorganization and nitrogen metabolism. Molecular modeling demonstrated stable glyphosate binding within catalytic domains of MMPs (affinities: -5.03 to - 6.29 kcal/mol), with dynamics simulations confirming persistent complex formation over 100 ns. Results indicate MMP-mediated dysregulation of structural homeostasis, alongside metabolic pathway perturbation, as contributory factors in glyphosate-associated renal pathology. The prominence of MMPs across target networks and functional analyses suggests their role as molecular conduits for glyphosate toxicity.

摘要

通过整合网络毒理学、分子对接和动力学模拟,研究了草甘膦诱导的肾毒性和致癌性的分子机制。筛选确定了47个潜在的草甘膦靶点;交叉分析产生了20个肾损伤和31个肾癌共同靶点。蛋白质-蛋白质相互作用网络突出了基质金属蛋白酶(MMP9、MMP2、MMP8、MMP3)和纤溶酶原(PLG)作为拓扑中心。通路富集揭示了细胞外基质重组和氮代谢的显著变化。分子建模表明草甘膦在MMPs催化域内稳定结合(亲和力:-5.03至-6.29千卡/摩尔),动力学模拟证实了在100纳秒以上持续形成复合物。结果表明,MMP介导的结构稳态失调以及代谢途径扰动是草甘膦相关肾脏病理的促成因素。MMPs在靶标网络和功能分析中的突出地位表明它们作为草甘膦毒性分子传导途径的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cb0/12375789/897f695e2af7/41598_2025_17067_Fig1_HTML.jpg

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