Size dependent nephrotoxicity of polystyrene microplastics revealed by single-cell transcriptomics profiling

Abstract

Microplastics (MPs) are emerging environmental contaminants with growing concern over their potential nephrotoxicity. However, their size-dependent effects on kidney function remain poorly understood. Here, we employed single-cell RNA sequencing (scRNA-seq) to systematically investigate the renal cellular responses to polystyrene microplastics (PS-MPs) of different sizes (50 nm, 500 nm, and 5 μm). Our results revealed that proximal tubular (PT) cells and renal immune cells are the primary targets of PS-MPs, exhibiting distinct transcriptomic and functional alterations. Medium- and large-sized particles induced stronger inflammatory responses, oxidative stress, ATP depletion, and apoptosis compared to smaller ones. STAT1 was identified as a key regulator mediating size-dependent inflammation in PT cells, and its knockdown significantly attenuated PS-MPs-induced injury. Immune cells profiling further showed particle size-specific activation patterns, with macrophages and cytotoxic T cells displaying pronounced pro-inflammatory and cytotoxic responses. These findings highlight the importance of particle size in dictating microplastic toxicity and underscore the need for size-specific safety evaluations. This study provides novel mechanistic insights into MPs-induced renal injury and identifies STAT1 as a potential therapeutic target.