Integrative Analysis of Pharmacology and Transcriptomics Predicts Resveratrol Will Ameliorate Microplastics-Induced Lung Damage by Targeting Ccl2 and Esr1

Abstract

Background: Microplastics (MPs) are ubiquitous on earth, posing a growing threat to human health. Previous studies have shown that the lung is a primary organ for MPs exposure. Resveratrol (RES) is a common dietary polyphenol that exhibits anti-inflammatory and antioxidant effects. However, whether RES exerts a protective effect against MPs-induced lung damage is still unknown. Methods: The targets of RES were retrieved from five databases. Differentially expressed genes (DEGs) were identified through comprehensive bioinformatic analysis. Multiple algorithms were employed to screen for the core targets. Ultimately, molecular docking analysis and molecular dynamics (MD) simulations were utilized to confirm the binding affinity between RES and the core targets. Results: In total, 1235 DEGs were identified in the transcriptomes. After removing duplicates, a total of 739 RES targets were obtained from five databases, and 66 of these targets intersected with DEGs. The potential core targets (Esr1, Ccl2) were further identified through topological analysis and machine learning. These findings were subsequently verified by molecular docking and MD simulations. Conclusions: This study demonstrated that RES may mitigate lung injury induced by MPs by targeting Esr1 and Ccl2. Our research offers a novel perspective on the prevention and treatment of MPs-induced lung injury.