ArticleComputational and structural biotechnology journal2024
Toxicogenomic assessment of in vitro macrophages exposed to profibrotic challenge reveals a sustained transcriptomic immune signature.
Article in Computational and structural biotechnology journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Review on Predictive Models and Integration Strategies for Holistic Impact Assessment of Chemicals and Materials.Environmental science & technology · 2026Review
- Integrated Approaches in Drug Repositioning Highlight Ouabain and Helenalin as Potential Drug Candidates for Pulmonary Fibrosis.Computational and structural biotechnology journal · 2026Article
- BMDx2: A Tool for Integrating Toxicogenomics-Based Dose-Dependency Analysis and AOP-Based Mechanistic Insights.Small methods · 2025Article
- Endothelial sensitivity to pro-fibrotic signals links systemic exposure to pulmonary fibrosis.Cell death & disease · 2025Article
- CHIASMA: Advancing chemicals and materials safety and sustainability assessments through innovative integration of in vitro and in silico (new approach) methodologies.Computational and structural biotechnology journal · 2025Article
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Authors and funding
10 authors.
Funding
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Abstract
Immune signalling is a crucial component in the progression of fibrosis. However, approaches for the safety assessment of potentially profibrotic substances, that provide information on mechanistic immune responses, are underdeveloped. This study aimed to develop a novel framework for assessing the immunotoxicity of fibrotic compounds. We exposed macrophages in vitro to multiple sublethal concentrations of the profibrotic agent bleomycin, over multiple timepoints, and generated RNA sequencing data. Using a toxicogenomic approach, we performed dose-dependent analysis to discover genes dysregulated by bleomycin exposure in a dose-responsive manner. A subset of immune genes displayed a sustained dose-dependent and differential expression response to profibrotic challenge. An immunoassay revealed cytokines and proteinases responding to bleomycin exposure that closely correlated to transcriptomic alterations, underscoring the integration between transcriptional immune response and external immune signalling activity. This study not only increases our understanding of the immunological mechanisms of fibrosis, but also offers an innovative framework for the toxicological evaluation of substances with potential fibrogenic effects on macrophage signalling. Our work brings a new immunotoxicogenomic direction for hazard assessment of fibrotic compounds, through the implementation of a time and resource efficient in vitro methodology.
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