Diesel particulate matter-induced proteomic changes in three-dimensional spheroids derived from human primary cells of various tissue origins

Abstract

This study investigated the effects of diesel particulate matter (DPM) on multiple human organs using 3D spheroids derived from eight human primary cell types. To assess the impact of DPM, we exposed these spheroids to varying concentrations of standardized DPM (Standard Reference Material, SRM 2975) and measured their viability, followed by proteomic analysis using tandem mass tag (TMT) labeling with liquid chromatography？tandem mass spectrometry (LC-MS/MS). A total of 9,707 proteins were identified, with 128 proteins exhibiting statistically significant changes (P-value？<？0.05) in response to DPM exposure, as determined by two-way analysis of variance (ANOVA). Among these, five proteins, including apolipoprotein A-I (APOA1), significantly increased at higher DPM concentrations, while 36 proteins, primarily ribosomal proteins, showed notable decreases even at lower DPM levels. Canonical pathway analysis revealed activation of acute phase response signaling, liver X receptor/retinoid X receptor (LXR/RXR), and farnesoid X receptor (FXR)/RXR pathways across all spheroid types. APOA1 was identified as a potential biomarker for DPM exposure, with increased expression potentially linked to disruption in protein degradation pathways. This study provides valuable insights into the systemic toxicity of DPM, highlighting key proteomic changes across different tissue types and identifying potential biomarkers that could be used to assess exposure levels and health risks related to particulate matter.