{"title":"对暴露于损伤性挑战的体外巨噬细胞进行的毒物基因组学评估揭示了持续的转录组免疫特征","authors":"","doi":"10.1016/j.csbj.2024.10.010","DOIUrl":null,"url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":10715,"journal":{"name":"Computational and structural biotechnology journal","volume":null,"pages":null},"PeriodicalIF":4.4000,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Toxicogenomic assessment of in vitro macrophages exposed to profibrotic challenge reveals a sustained transcriptomic immune signature\",\"authors\":\"\",\"doi\":\"10.1016/j.csbj.2024.10.010\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>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.</div></div>\",\"PeriodicalId\":10715,\"journal\":{\"name\":\"Computational and structural biotechnology journal\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2024-10-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Computational and structural biotechnology journal\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2001037024003301\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Computational and structural biotechnology journal","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2001037024003301","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Toxicogenomic assessment of in vitro macrophages exposed to profibrotic challenge reveals a sustained transcriptomic immune signature
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.
期刊介绍:
Computational and Structural Biotechnology Journal (CSBJ) is an online gold open access journal publishing research articles and reviews after full peer review. All articles are published, without barriers to access, immediately upon acceptance. The journal places a strong emphasis on functional and mechanistic understanding of how molecular components in a biological process work together through the application of computational methods. Structural data may provide such insights, but they are not a pre-requisite for publication in the journal. Specific areas of interest include, but are not limited to:
Structure and function of proteins, nucleic acids and other macromolecules
Structure and function of multi-component complexes
Protein folding, processing and degradation
Enzymology
Computational and structural studies of plant systems
Microbial Informatics
Genomics
Proteomics
Metabolomics
Algorithms and Hypothesis in Bioinformatics
Mathematical and Theoretical Biology
Computational Chemistry and Drug Discovery
Microscopy and Molecular Imaging
Nanotechnology
Systems and Synthetic Biology