Identification of the Hub Genes Linked to Lead (IV)-Induced Spleen Toxicity Using the Rat Model

Biol Trace Elem Res. 2023 Dec 28. doi: 10.1007/s12011-023-04036-w. Online ahead of print.

Abstract

Exposure to lead (Pb) has harmful effects on the organs of both humans and animals, particularly the spleen. However, the precise mechanisms through which Pb (IV) exposure leads to spleen toxicity remain unclear. Hence, this study aimed to identify the key genes and signaling pathways involved in spleen toxicity caused by Pb (IV) incubation. We obtained the dataset GSE59925 from the Gene Expression Omnibus, which included spleen samples treated with lead tetraacetate (PbAc4) as well as control samples on the 1st and 5th day. Through differential expression analysis, we identified 607 and 704 differentially expressed genes (DEGs) in the spleens on the 1st and 5th day following PbAc4 treatment, respectively, with 245 overlapping DEGs between the two time points. Gene ontology analysis revealed that the commonly shared DEGs were primarily involved in signal transduction, drug response, cell proliferation, adhesion, and migration. Pathway analysis indicated that the common DEGs were primarily associated with MAPK, TNF, cAMP, Hippo, and TGF-β signaling pathways. Furthermore, we identified the hub genes such as CXCL10, PARP1, APOE, and VDR contributing to PbAc4-induced spleen toxicity. This study enhances our understanding of the molecular mechanisms underlying Pb (IV) toxicity in the spleen.

Keywords: Gene; Pb (IV); Signaling pathway; Spleen toxicity.