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PM 2.5 , also known as fine particles, refers to particulate matter with a dynamic diameter of ≦2.5 μm in air pollutants, that carries metals (Zn, Co, Cd) which can pass through the alveolar epithelium and enter the circulatory system and tissues. PM 2.5  can cause serious health problems, such as non-alcoholic fatty liver and hepatocellular carcinoma, although the underlying mechanisms of its toxic effect are poorly understood. Here, we exposed L02 cells to PM 2.5  and performed a pooled genome−wide clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) to assess loss of function and identify new potential PM 2.5 targets. Enrichr and KEGG pathway analyses were performed to identify candidate genes associated with PM 2.5  toxicity. Results revealed that four key genes, namely ATPase Na+/K+ transporting subunit alpha 2 (ATP1A2), metallothionein 1M (MT1M), solute carrier family 6 members 19 (SLC6A19) and transient receptor potential cation channel subfamily V member 6 (TRPV6) were associated with PM 2.5  toxicity, mainly in regulating the mineral absorption pathway. Downregulating these genes increased cell viability and attenuated apoptosis in cells exposed to PM 2.5 . Conversely, overexpressing TRPV6 exacerbated cell apoptosis caused by PM 2.5 , while a reactive oxygen species (ROS) inhibitor N-acetyl-l-cysteine (NAC) alleviated PM 2.5 -induced apoptosis. In conclusion, ATP1A2, MT1M, SLC6A19 and TRPV6 may be contributing to absorption of metals in PM 2.5  thereby inducing apoptosis mediated by ROS. Therefore, they hold potential as therapeutic targets for PM 2.5 -related diseases.

frontiers in bioengineering and biotechnology

CRISPR/Cas9-Mediated Whole Genomic Wide Knockout Screening Identifies Specific Genes Associated With PM2.5-Induced Mineral Absorption in Liver Toxicity