Is Cadmium Toxicity Tissue-Specific? Toxicogenomics Studies Reveal Common and Specific Pathways in Pulmonary, Hepatic, and Neuronal Cell Models

Several harmful modifications in different tissues-organs, leading to relevant diseases (e.g., liver and lung diseases, neurodegeneration), are reported after exposure to cadmium (Cd), a wide en-vironmental contaminant. This aspect arises the question whether any common molecular sig-natures and/or Cd-induced modifications might represent the building block in initiating or contributing to address the cells towards different pathological conditions. To unravel a possible mechanism of Cd tissue-specificity, we have performed a comparison of transcriptomics data from cell models representative of three major Cd targets: pulmonary (A549), hepatic (HepG2), and neuronal (SH-SY-5Y) cells. The functional analysis of dysregulated genes shows cell and molecular targets, related to different functions and leading to different effects, which can be broadly grouped in 1) Stress response to metals and endoplasmic reticulum stress; 2) Cancer; 3) Immunoregulatory and inflammatory processes; 4) Ions regulators or regulated molecules, and 5) Response to or effectors of epigenetic changes. Results from KEGG analysis show that only one pathway is dysregulated in a significant way in all cell models: the mineral absorption pathway. Our data clearly indicate how the molecular mimicry of Cd and its ability to cause a general metal ions dyshomeostasis represent the initial common feature leading to different molecular signatures and alterations.

FORCELLA Matilde;  LAU POUI CHEUNG Pierre;  FABBRI Marco;  FUSI Paola;  OLDANI Monica;  MELCHIORETTO Pasquale;  GRIBALDO Laura;  URANI Chiara; 

2022-03-15

MDPI

JRC126579

1422-0067 (online),    1661-6596 (print),   

https://publications.jrc.ec.europa.eu/repository/handle/JRC126579,   

10.3390/ijms23031768 (online),