GSE107084
RNA sequencing analysis shows that titanium dioxide nanoparticles induce endoplasmic reticulum stress, which has a central role in mediating plasma glucose in mice
Titanium dioxide nanoparticles (TiO2 NPs) constitute the top five NPs in use today. A recent study determined that oral administration of TiO2 NPs increases plasma glucose in mice. In the current study, RNA sequencing (RNA-seq) technology was used to investigate genome-wide effects of TiO2 NPs. Clustering analysis of the RNA-seq data showed the most significantly enriched gene ontology terms and KEGG pathways related to the endoplasmic reticulum (ER) and ER stress. Molecular biology verification showed that TiO2 NPs activated a xenobiotic biodegradation response and increased expression of cytochrome P450 family genes in mouse livers, thus inducing ER stress in mice. ER stress activated MAPK and NF-?B pathways and induced an inflammation response, resulting in phosphorylation of the insulin receptor substrate 1 and, consequently, insulin resistance. This was the main mechanism by which TiO2 NPs increased plasma glucose in mice. Meanwhile, ER stress disturbed the monooxygenase system, and thus generated reactive oxygen species (ROS). Relief of ER stress with 4-phenylbutyric acid inhibited all the above effects of TiO2 NPs, including the generation of ROS. Therefore, TiO2 NP-induced ER stress was a decisive factor with a central role in plasma glucose disturbance in mice. Overall design: Examination of genome-wide expressions in Control and NP groups