In Silico Transcriptomic Analysis Suggests That Nickel Exposure Upregulates NINJ1 Expression: Implications for Lytic...

Nickel (Ni) has been shown to induce cell death in multiple studies, by the involvement of different programmed cell death mechanisms such as apoptosis and pyroptosis. NINJ1 (Ninjurin 1) is a recently identified transmembrane protein, mediating plasma membrane rupture and the loss of plasma membrane integrity during lytic cell death or following mechanical strain. The involvement of NINJ1-mediated plasma membrane rupture in nickel-induced cell death has not been previously studied. Here, by performing in silico transcriptomics analysis of publicly available datasets in the R programming environment, we observed that nickel exposure/treatment increases the expression of NINJ1 at the transcription (mRNA) level in various cell types such as human PBMCs and endothelial cells, and rat liver cells (fold changes of 1.1, 2.61, and 1.02, respectively). Besides, we observed that in skin biopsies of individuals who were exposed to nickel, those with nickel allergy have higher NINJ1 mRNA expression compared to those without nickel allergy (nonallergic controls) (fold change of around 1.05), pointing to the potential involvement of NINJ1 in nickel allergy in skin. Combined, based on computational data analyses, we here hypothesized that nickel-induced increases in NINJ1 mRNA expression might possibly lead to higher levels of NINJ1-mediated plasma membrane rupture and lytic cell death in these nickel-exposed cells, likely resulting in increased inflammation. However, since this bioinformatics study is solely based on computational reanalysis, and functional NINJ1-mediated plasma membrane rupture following nickel exposure was not experimentally demonstrated, additional experimental data is required to support the findings. Further research is needed to identify cellular mechanisms by which nickel induces NINJ1 mRNA expression and possibly lytic cell death, contributing to the nickel-induced inflammation.