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Signaling Pathways and Genes Associated with Hexavalent Chromium-Induced Hepatotoxicity

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Abstract

Exposure to hexavalent chromium [Cr(VI)] causes human and animal hepatotoxicity. However, it is unclear how Cr(VI) induces hepatotoxicity, nor is it clear which pathways and genes may be involved. This study aimed to identify the key molecular pathways and genes engaged in Cr(VI)-induced hepatotoxicity. Publicly available microarray GSE19662 was downloaded from the Gene Expression Omnibus database. GSE19662 consists of primary rat hepatocyte (PRH) groups treated with or without 0.10 ppm potassium dichromate (PD), with three samples per group. Compared to the control group, a total of 400 differentially expressed genes were obtained. Specially 262 and 138 genes were up- and downregulated in PD-treated PRHs, respectively. Gene ontology (GO) enrichment indicated that those DEGs were primarily engaged in many biological processes, including androgen biosynthetic process, the positive regulation of cell death, the response to activity, the toxic substance and hepatocyte growth factor stimulus, and others. Kyoto Encyclopedia of Genes and Genomes (KEGG) suggested that the DEGs are fundamentally enriched in hepatocellular carcinoma (HCC), hepatitis B, p53, PI3K-Akt, MAPK, AMPK, metabolic pathways, estrogen, cGMP-PKG, metabolic pathways, etc. Moreover, many genes, including UBE2C, TOP2A, PRC1, CENPF, and MKI67, might contribute to Cr(VI)-induced hepatotoxicity. Taken together, this study enhances our understanding of the regulation, prevention, and treatment strategies of Cr(VI)-induced hepatotoxicity.

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Funding

This study was supported by the Talent Introduction Program of Anhui Science and Technology University (No. DKYJ202003).

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Authors and Affiliations

  1. College of Animal Science, Anhui Science and Technology University, Fengyang, 233100, China

    Xiaofeng Li & Bing Yang

  2. Biological Applications Department, Nuclear Research Center, Egyptian Atomic Energy Authority, Abu-Zaabal, 13759, Egypt

    Abdel-Moneim Eid Abdel-Moneim

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  1. Xiaofeng Li
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  3. Bing Yang
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Contributions

B Yang designed the study. EA Abdel-Moneim reviewed the manuscript and revised the scientific English. XF Li wrote this manuscript and performed the bioinformatics analysis. The authors reviewed this manuscript.

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Correspondence to Bing Yang.

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Additional file 1:

All transcripts identified in PRHs of PD-treated and control groups. (XLSX = 3, 032 KB)

Additional file 2:

All genes identified in PRHs of PD-treated and control groups. (XLSX = 1, 318 KB)

Additional file 3:

All DETs in PRHs between PD-treated and control groups. (XLSX = 86 KB)

Additional file 4:

All DEGs in PRHs between PD-treated and control groups. (XLSX = 48 KB)

Additional file 5:

GO analysis for DEGs in PRHs between PD-treated and control groups. (XLSX = 24 KB)

Additional file 6:

KEGG analysis for DEGs in PRHs between PD-treated and control groups. (XLSX = 18 KB)

Additional file 7:

Reactome analysis for DEGs in PRHs between PD-treated and control groups. (XLSX = 16 KB)

Additional file 8:

PANTHER analysis for DEGs in PRHs between PD-treated and control groups. (XLSX = 11 KB)

Additional file 9:

Protein classification for DEGs in PRHs between PD-treated and control groups. (XLSX = 11 KB)

Additional file 10:

GO analysis for hub genes associated with PD-induced hepatotoxicity. (XLSX = 11 KB)

Additional file 11:

KEGG analysis for hub genes associated with PD-induced hepatotoxicity. (XLSX = 11 KB)

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Li, X., Abdel-Moneim, AM.E. & Yang, B. Signaling Pathways and Genes Associated with Hexavalent Chromium-Induced Hepatotoxicity. Biol Trace Elem Res 201, 1888–1904 (2023). https://doi.org/10.1007/s12011-022-03291-7

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