Multi-walled carbon nanotubes elicit concordant changes in DNA methylation and gene expression following long-term pulmonary exposure in mice

Giovanni Scala; Mathilde N. Delaval; Sourav P. Mukherjee; Antonio Federico; Timur O. Khaliullin; Naveena Yanamala; Liliya M. Fatkhutdinova; Elena R. Kisin; Dario Greco; Bengt Fadeel; Anna A. Shvedova

doi:10.1016/j.carbon.2021.03.045

Multi-walled carbon nanotubes elicit concordant changes in DNA methylation and gene expression following long-term pulmonary exposure in mice

Giovanni Scala
, Mathilde N. Delaval
, Sourav P. Mukherjee
, Antonio Federico
, Timur O. Khaliullin
, Naveena Yanamala
, Liliya M. Fatkhutdinova
, Elena R. Kisin
, Dario Greco
, Bengt Fadeel^*
, Anna A. Shvedova

^*Corresponding author for this work

Research output: Contribution to journal › Article › Scientific › peer-review

15 Citations (Scopus)

23 Downloads (Pure)

Abstract

Pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) causes inflammation and fibrosis. Our previous work has shown that industrially produced MWCNTs trigger specific changes in gene expression in the lungs of exposed animals. To elucidate whether epigenetic effects play a role for these gene expression changes, we performed whole genome bisulphite sequencing to assess DNA methylation patterns in the lungs 56 days after exposure to MWCNTs. Lung tissues were also evaluated with respect to histopathological changes and cytokine profiling of bronchoalveolar lavage (BAL) fluid was conducted using a multi-plex array. Integrated analysis of transcriptomics data and DNA methylation data revealed concordant changes in gene expression. Functional analysis showed that the muscle contraction, immune system/inflammation, and extracellular matrix pathways were the most affected pathways. Taken together, the present study revealed that MWCNTs exert epigenetic effects in the lungs of exposed animals, potentially driving the subsequent gene expression changes.

Original language	English
Pages (from-to)	563-572
Number of pages	10
Journal	Carbon
Volume	178
Early online date	Mar 2021
DOIs	https://doi.org/10.1016/j.carbon.2021.03.045
Publication status	Published - 30 Jun 2021
Publication type	A1 Journal article-refereed

Funding

This study was supported by the European Commission through the Seventh Framework Programme (FP7-NANOMMUNE, grant agreement no. 214281), and the Nanotechnology Research Center of the National Institute for Occupational Safety and Health (NTRC 939011K). DG was supported by the Academy of Finland (grant agreement no. 322761). We thank the SNP&SEQ Technology Platform at Uppsala University, Uppsala, Sweden, for assistance with the whole genome bisulphite sequencing. The SNP&SEQ platform is part of the National Genomics Infrastructure (NGI) and Science for Life Laboratory and is supported by the Swedish Research Council and by the Knut and Alice Wallenberg Foundation.

Keywords

Carbon nanotubes
DNA methylation
Epigenetics
Inflammation
Transcriptomics

Publication forum classification

Publication forum level 2

ASJC Scopus subject areas

General Chemistry
General Materials Science

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10.1016/j.carbon.2021.03.045Licence: CC BY

1-s2.0-S0008622321003511-mainFinal published version, 1.63 MBLicence: CC BY

http://urn.fi/URN:NBN:fi:tuni-202105034240Licence: CC BY

Cite this

Scala, G., Delaval, M. N., Mukherjee, S. P., Federico, A., Khaliullin, T. O., Yanamala, N., Fatkhutdinova, L. M., Kisin, E. R., Greco, D., Fadeel, B., & Shvedova, A. A. (2021). Multi-walled carbon nanotubes elicit concordant changes in DNA methylation and gene expression following long-term pulmonary exposure in mice. Carbon, 178, 563-572. https://doi.org/10.1016/j.carbon.2021.03.045

@article{a4e55da864ba4dba8e07593ece500244,

title = "Multi-walled carbon nanotubes elicit concordant changes in DNA methylation and gene expression following long-term pulmonary exposure in mice",

abstract = "Pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) causes inflammation and fibrosis. Our previous work has shown that industrially produced MWCNTs trigger specific changes in gene expression in the lungs of exposed animals. To elucidate whether epigenetic effects play a role for these gene expression changes, we performed whole genome bisulphite sequencing to assess DNA methylation patterns in the lungs 56 days after exposure to MWCNTs. Lung tissues were also evaluated with respect to histopathological changes and cytokine profiling of bronchoalveolar lavage (BAL) fluid was conducted using a multi-plex array. Integrated analysis of transcriptomics data and DNA methylation data revealed concordant changes in gene expression. Functional analysis showed that the muscle contraction, immune system/inflammation, and extracellular matrix pathways were the most affected pathways. Taken together, the present study revealed that MWCNTs exert epigenetic effects in the lungs of exposed animals, potentially driving the subsequent gene expression changes.",

keywords = "Carbon nanotubes, DNA methylation, Epigenetics, Inflammation, Transcriptomics",

author = "Giovanni Scala and Delaval, \{Mathilde N.\} and Mukherjee, \{Sourav P.\} and Antonio Federico and Khaliullin, \{Timur O.\} and Naveena Yanamala and Fatkhutdinova, \{Liliya M.\} and Kisin, \{Elena R.\} and Dario Greco and Bengt Fadeel and Shvedova, \{Anna A.\}",

note = "Funding Information: This study was supported by the European Commission through the Seventh Framework Programme (FP7-NANOMMUNE, grant agreement no. 214281), and the Nanotechnology Research Center of the National Institute for Occupational Safety and Health (NTRC 939011K). DG was supported by the Academy of Finland (grant agreement no. 322761). We thank the SNP\&SEQ Technology Platform at Uppsala University, Uppsala, Sweden, for assistance with the whole genome bisulphite sequencing. The SNP\&SEQ platform is part of the National Genomics Infrastructure (NGI) and Science for Life Laboratory and is supported by the Swedish Research Council and by the Knut and Alice Wallenberg Foundation. Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = jun,

day = "30",

doi = "10.1016/j.carbon.2021.03.045",

language = "English",

volume = "178",

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Scala, G, Delaval, MN, Mukherjee, SP, Federico, A, Khaliullin, TO, Yanamala, N, Fatkhutdinova, LM, Kisin, ER, Greco, D, Fadeel, B & Shvedova, AA 2021, 'Multi-walled carbon nanotubes elicit concordant changes in DNA methylation and gene expression following long-term pulmonary exposure in mice', Carbon, vol. 178, pp. 563-572. https://doi.org/10.1016/j.carbon.2021.03.045

TY - JOUR

T1 - Multi-walled carbon nanotubes elicit concordant changes in DNA methylation and gene expression following long-term pulmonary exposure in mice

AU - Scala, Giovanni

AU - Delaval, Mathilde N.

AU - Mukherjee, Sourav P.

AU - Federico, Antonio

AU - Khaliullin, Timur O.

AU - Yanamala, Naveena

AU - Fatkhutdinova, Liliya M.

AU - Kisin, Elena R.

AU - Greco, Dario

AU - Fadeel, Bengt

AU - Shvedova, Anna A.

N1 - Funding Information: This study was supported by the European Commission through the Seventh Framework Programme (FP7-NANOMMUNE, grant agreement no. 214281), and the Nanotechnology Research Center of the National Institute for Occupational Safety and Health (NTRC 939011K). DG was supported by the Academy of Finland (grant agreement no. 322761). We thank the SNP&SEQ Technology Platform at Uppsala University, Uppsala, Sweden, for assistance with the whole genome bisulphite sequencing. The SNP&SEQ platform is part of the National Genomics Infrastructure (NGI) and Science for Life Laboratory and is supported by the Swedish Research Council and by the Knut and Alice Wallenberg Foundation. Publisher Copyright: © 2021 The Authors

PY - 2021/6/30

Y1 - 2021/6/30

N2 - Pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) causes inflammation and fibrosis. Our previous work has shown that industrially produced MWCNTs trigger specific changes in gene expression in the lungs of exposed animals. To elucidate whether epigenetic effects play a role for these gene expression changes, we performed whole genome bisulphite sequencing to assess DNA methylation patterns in the lungs 56 days after exposure to MWCNTs. Lung tissues were also evaluated with respect to histopathological changes and cytokine profiling of bronchoalveolar lavage (BAL) fluid was conducted using a multi-plex array. Integrated analysis of transcriptomics data and DNA methylation data revealed concordant changes in gene expression. Functional analysis showed that the muscle contraction, immune system/inflammation, and extracellular matrix pathways were the most affected pathways. Taken together, the present study revealed that MWCNTs exert epigenetic effects in the lungs of exposed animals, potentially driving the subsequent gene expression changes.

AB - Pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) causes inflammation and fibrosis. Our previous work has shown that industrially produced MWCNTs trigger specific changes in gene expression in the lungs of exposed animals. To elucidate whether epigenetic effects play a role for these gene expression changes, we performed whole genome bisulphite sequencing to assess DNA methylation patterns in the lungs 56 days after exposure to MWCNTs. Lung tissues were also evaluated with respect to histopathological changes and cytokine profiling of bronchoalveolar lavage (BAL) fluid was conducted using a multi-plex array. Integrated analysis of transcriptomics data and DNA methylation data revealed concordant changes in gene expression. Functional analysis showed that the muscle contraction, immune system/inflammation, and extracellular matrix pathways were the most affected pathways. Taken together, the present study revealed that MWCNTs exert epigenetic effects in the lungs of exposed animals, potentially driving the subsequent gene expression changes.

KW - Carbon nanotubes

KW - DNA methylation

KW - Epigenetics

KW - Inflammation

KW - Transcriptomics

U2 - 10.1016/j.carbon.2021.03.045

DO - 10.1016/j.carbon.2021.03.045

M3 - Article

AN - SCOPUS:85103416147

SN - 0008-6223

VL - 178

SP - 563

EP - 572

JO - Carbon

JF - Carbon

ER -

Multi-walled carbon nanotubes elicit concordant changes in DNA methylation and gene expression following long-term pulmonary exposure in mice

Abstract

Funding

Keywords

Publication forum classification

ASJC Scopus subject areas

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