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纳米颗粒的祖先分子反应。

An ancestral molecular response to nanomaterial particulates.

机构信息

FHAIVE, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

Tampere Institute for Advanced Study, Tampere, Finland.

出版信息

Nat Nanotechnol. 2023 Aug;18(8):957-966. doi: 10.1038/s41565-023-01393-4. Epub 2023 May 8.

DOI:10.1038/s41565-023-01393-4
PMID:37157020
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10427433/
Abstract

The varied transcriptomic response to nanoparticles has hampered the understanding of the mechanism of action. Here, by performing a meta-analysis of a large collection of transcriptomics data from various engineered nanoparticle exposure studies, we identify common patterns of gene regulation that impact the transcriptomic response. Analysis identifies deregulation of immune functions as a prominent response across different exposure studies. Looking at the promoter regions of these genes, a set of binding sites for zinc finger transcription factors CH, involved in cell stress responses, protein misfolding and chromatin remodelling and immunomodulation, is identified. The model can be used to explain the outcomes of mechanism of action and is observed across a range of species indicating this is a conserved part of the innate immune system.

摘要

对纳米颗粒的转录组反应的多样性阻碍了对其作用机制的理解。在这里，通过对来自各种工程纳米颗粒暴露研究的大量转录组学数据进行荟萃分析，我们确定了影响转录组反应的常见基因调控模式。分析确定免疫功能失调是不同暴露研究中突出的反应。观察这些基因的启动子区域，确定了一组锌指转录因子 CH 的结合位点，这些转录因子参与细胞应激反应、蛋白质错误折叠、染色质重塑和免疫调节。该模型可用于解释作用机制的结果，并在一系列物种中观察到，表明这是先天免疫系统的一个保守部分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4889/10427433/15faf7b462fa/41565_2023_1393_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4889/10427433/5ac9b65e0d82/41565_2023_1393_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4889/10427433/25c6c8e57ebe/41565_2023_1393_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4889/10427433/3aa221c27d69/41565_2023_1393_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4889/10427433/7ef1d4d8589e/41565_2023_1393_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4889/10427433/649be1a4089c/41565_2023_1393_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4889/10427433/15faf7b462fa/41565_2023_1393_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4889/10427433/5ac9b65e0d82/41565_2023_1393_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4889/10427433/25c6c8e57ebe/41565_2023_1393_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4889/10427433/3aa221c27d69/41565_2023_1393_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4889/10427433/7ef1d4d8589e/41565_2023_1393_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4889/10427433/649be1a4089c/41565_2023_1393_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4889/10427433/15faf7b462fa/41565_2023_1393_Fig6_HTML.jpg

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An ancestral molecular response to nanomaterial particulates.

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本文引用的文献

[1]
Toxicogenomics Data for Chemical Safety Assessment and Development of New Approach Methodologies: An Adverse Outcome Pathway-Based Approach.

Adv Sci (Weinh). 2023-1

[2]
Comparative Toxicogenomics Database (CTD): update 2023.

Nucleic Acids Res. 2023-1-6

[3]
ToxPoint: Copper Is the New Showstopper.

Toxicol Sci. 2022-8-25

[4]
Characterization of ENM Dynamic Dose-Dependent MOA in Lung with Respect to Immune Cells Infiltration.

Nanomaterials (Basel). 2022-6-13

[5]
Cross-species transcriptomic signatures identify mechanisms related to species sensitivity and common responses to nanomaterials.

Nat Nanotechnol. 2022-6

[6]
Environmentally sensitive hotspots in the methylome of the early human embryo.

Elife. 2022-2-21

[7]
Prospects and challenges for FAIR toxicogenomics data.

Nat Nanotechnol. 2022-1

[8]
Epigenetic memories and the evolution of infectious diseases.

Nat Commun. 2021-7-13

[9]
Extrapolating from acute to chronic toxicity in vitro.

Toxicol In Vitro. 2021-10

[10]
First principles characterisation of bio-nano interface.

Phys Chem Chem Phys. 2021-6-23

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