What question did this study set out to answer?

The aim is to investigate the effect of nickel on NINJ1 expression and its potential role in cell death mechanisms.

April 28, 2026Environmental Toxicology0 citations

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

SASukran Yagmur AvciogluTokat Gaziosmanpaşa Üniversitesi BÖBüşra Nur ÖzdemirÇanakkale Onsekiz Mart Üniversitesi CBCaglar Berkel

Key Points

The aim is to investigate the effect of nickel on NINJ1 expression and its potential role in cell death mechanisms.
Performed in silico transcriptomic analysis using publicly available datasets in R programming environment.
Analyzed gene expression changes in nickel-exposed human PBMCs, endothelial cells, and rat liver cells.
Compared NINJ1 expression in skin biopsies of nickel-exposed individuals with and without allergy.
Nickel exposure significantly increased NINJ1 mRNA expression in human PBMCs (fold change 1.1), endothelial cells (fold change 2.61), and rat liver cells (fold change 1.02).
Individuals with nickel allergy exhibited higher NINJ1 mRNA expression (fold change ~1.05) compared to nonallergic controls.
Hypothesized that increased NINJ1 expression may lead to higher lytic cell death and inflammation in nickel-exposed cells.

Abstract

ABSTRACT 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.

问 AI

Bookmark

View Full Paper