image: This illustration outlines the comprehensive research strategy combining computational biology, machine learning, and experimental validation. Using network toxicology, 238 overlapping targets were identified from 374 PS-related targets and 4,037 kidney injury-related targets, and a protein-protein interaction (PPI) network was constructed. Machine learning was employed to screen for pivotal genes, and molecular docking coupled with molecular dynamics simulations were utilized to validate the binding between PS and core targets (e.g., MMP9, APP). Single-cell transcriptome analysis further uncovered the critical role of intercellular communication. The central mechanistic discovery: PS upregulates Amyloid Precursor Protein (APP), which acts as a ligand engaging CD74 and PTGER2 receptors on endothelial cells. This interaction promotes aberrant communication between endothelial cells and immune cells (e.g., NK cells), ultimately contributing to glomerulonephritis, renal tubular cell damage, and fibrosis. Finally, in vitro experiments—including CCK-8 cell viability assay, wound healing assay, and Western blot—using human renal tubular epithelial cells (HK-2) confirmed the cytotoxicity of PS, its inhibitory effect on cell migration, and the upregulation of APP protein expression.
Credit: Yimao Wu and Meng-Yao Li
Potassium sorbate is widely used as a preservative in processed foods and beverages and is generally considered safe. However, emerging evidence suggests potential health risks with long-term or high-level exposure. A study published on November 23, 2025, in iMetaMed provides the first systematic evidence that this common additive can induce acute kidney injury through molecular mechanisms involving oxidative stress, inflammation, and dysregulated cell-to-cell communication.
The research team, led by scientists from Shanghai Jiao Tong University School of Medicine and Guangdong Medical University, applied a multi-disciplinary strategy to uncover how potassium sorbate damages renal tissue. They began by predicting potential targets using network toxicology, then validated interactions through molecular docking and dynamics simulations. Machine learning algorithms further prioritized key genes from clinical datasets.
Among the top candidates, amyloid precursor protein emerged as a central regulator. Single-cell RNA sequencing analysis of human kidney tissues revealed that APP mediates communication between endothelial cells and immune cells—such as monocytes and natural killer cells—through the APP-CD74 and APP-PTGER2 ligand-receptor pairs.
“This is the first time that APP has been implicated in potassium sorbate-induced kidney injury, and the first evidence that it facilitates endothelial-immune crosstalk in a toxicological context,” said corresponding author Dr. Meng-Yao Li. “Our findings provide a cellular mechanism that helps explain how a common food additive could trigger renal inflammation and functional decline.”
In vitro experiments using human renal tubular cells confirmed that potassium sorbate exposure significantly reduced cell viability, inhibited migration—a key repair process—and upregulated APP protein expression in a dose-dependent manner.
The study also identified other key targets, including MMP9 and SIRT1, and highlighted relevant pathways such as lipid metabolism, atherosclerosis, and the AGE-RAGE signaling cascade, which are known to be involved in kidney disease progression.
These findings not only advance the understanding of food additive safety but also establish a new methodology for evaluating environmental toxin risks using multi-optic and computational tools.
Journal
iMeta
Method of Research
Experimental study
Subject of Research
Not applicable
Article Title
Potassium Sorbate Triggers Kidney Injury via Dysregulated Intercellular Communication: A Study Combining Network Toxicology, Machine Learning, Molecular Docking, and Single-Cell RNA Sequencing
Article Publication Date
23-Nov-2025
COI Statement
The authors declare no conflicts of interest.