Ex Vivo Human Colon Tissue Exposure to Pristine Graphene Activates Genes Involved in the Binding, Adhesion and Proliferation of Epithelial Cells

Toxicology studies on pristine graphene are limited and lack significant correlations with actual human response. The goal of the current study was to determine the response of total colonic human tissue to pristine graphene exposure. Biopsy punches of colon tissues from healthy human were used to a...

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Autores principales:	Mohamed H. Lahiani, Kuppan Gokulan, Katherine Williams, Sangeeta Khare
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	graphene nanomaterial toxicity risk assessment nonanimal model Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/f7e398b354564c768360f97f7975b341
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spelling	oai:doaj.org-article:f7e398b354564c768360f97f7975b3412021-11-11T16:54:25ZEx Vivo Human Colon Tissue Exposure to Pristine Graphene Activates Genes Involved in the Binding, Adhesion and Proliferation of Epithelial Cells10.3390/ijms2221114431422-00671661-6596https://doaj.org/article/f7e398b354564c768360f97f7975b3412021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11443https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Toxicology studies on pristine graphene are limited and lack significant correlations with actual human response. The goal of the current study was to determine the response of total colonic human tissue to pristine graphene exposure. Biopsy punches of colon tissues from healthy human were used to assess the biological response after ex vivo exposure to graphene at three different concentrations (1, 10, and 100 µg/mL). mRNA expression of specific genes or intestinal cytokine abundance was assessed using real-time PCR or multiplex immunoassays, respectively. Pristine graphene-activated genes that are related to binding and adhesion (<i>GTPase</i> and <i>KRAS</i>) within 2 h of exposure. Furthermore, the <i>PCNA</i> (proliferating cell nuclear antigen) gene was upregulated after exposure to graphene at all concentrations. Ingenuity pathway analysis revealed that STAT3 and VEGF signaling pathways (known to be involved in cell proliferation and growth) were upregulated. Graphene exposure (10 µg/mL) for 24 h significantly increased levels of pro-inflammatory cytokines IFNγ, IL-8, IL-17, IL-6, IL-9, MIP-1α, and Eotaxin. Collectively, these results indicated that graphene may activate the STAT3–IL23–IL17 response axis. The findings in this study provide information on toxicity evaluation using a human-relevant ex vivo colon model and serve as a basis for further exploration of its bio-applications.Mohamed H. LahianiKuppan GokulanKatherine WilliamsSangeeta KhareMDPI AGarticlegraphenenanomaterialtoxicityrisk assessmentnonanimal modelBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11443, p 11443 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	graphene nanomaterial toxicity risk assessment nonanimal model Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	graphene nanomaterial toxicity risk assessment nonanimal model Biology (General) QH301-705.5 Chemistry QD1-999 Mohamed H. Lahiani Kuppan Gokulan Katherine Williams Sangeeta Khare Ex Vivo Human Colon Tissue Exposure to Pristine Graphene Activates Genes Involved in the Binding, Adhesion and Proliferation of Epithelial Cells
description	Toxicology studies on pristine graphene are limited and lack significant correlations with actual human response. The goal of the current study was to determine the response of total colonic human tissue to pristine graphene exposure. Biopsy punches of colon tissues from healthy human were used to assess the biological response after ex vivo exposure to graphene at three different concentrations (1, 10, and 100 µg/mL). mRNA expression of specific genes or intestinal cytokine abundance was assessed using real-time PCR or multiplex immunoassays, respectively. Pristine graphene-activated genes that are related to binding and adhesion (<i>GTPase</i> and <i>KRAS</i>) within 2 h of exposure. Furthermore, the <i>PCNA</i> (proliferating cell nuclear antigen) gene was upregulated after exposure to graphene at all concentrations. Ingenuity pathway analysis revealed that STAT3 and VEGF signaling pathways (known to be involved in cell proliferation and growth) were upregulated. Graphene exposure (10 µg/mL) for 24 h significantly increased levels of pro-inflammatory cytokines IFNγ, IL-8, IL-17, IL-6, IL-9, MIP-1α, and Eotaxin. Collectively, these results indicated that graphene may activate the STAT3–IL23–IL17 response axis. The findings in this study provide information on toxicity evaluation using a human-relevant ex vivo colon model and serve as a basis for further exploration of its bio-applications.
format	article
author	Mohamed H. Lahiani Kuppan Gokulan Katherine Williams Sangeeta Khare
author_facet	Mohamed H. Lahiani Kuppan Gokulan Katherine Williams Sangeeta Khare
author_sort	Mohamed H. Lahiani
title	Ex Vivo Human Colon Tissue Exposure to Pristine Graphene Activates Genes Involved in the Binding, Adhesion and Proliferation of Epithelial Cells
title_short	Ex Vivo Human Colon Tissue Exposure to Pristine Graphene Activates Genes Involved in the Binding, Adhesion and Proliferation of Epithelial Cells
title_full	Ex Vivo Human Colon Tissue Exposure to Pristine Graphene Activates Genes Involved in the Binding, Adhesion and Proliferation of Epithelial Cells
title_fullStr	Ex Vivo Human Colon Tissue Exposure to Pristine Graphene Activates Genes Involved in the Binding, Adhesion and Proliferation of Epithelial Cells
title_full_unstemmed	Ex Vivo Human Colon Tissue Exposure to Pristine Graphene Activates Genes Involved in the Binding, Adhesion and Proliferation of Epithelial Cells
title_sort	ex vivo human colon tissue exposure to pristine graphene activates genes involved in the binding, adhesion and proliferation of epithelial cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f7e398b354564c768360f97f7975b341
work_keys_str_mv	AT mohamedhlahiani exvivohumancolontissueexposuretopristinegrapheneactivatesgenesinvolvedinthebindingadhesionandproliferationofepithelialcells AT kuppangokulan exvivohumancolontissueexposuretopristinegrapheneactivatesgenesinvolvedinthebindingadhesionandproliferationofepithelialcells AT katherinewilliams exvivohumancolontissueexposuretopristinegrapheneactivatesgenesinvolvedinthebindingadhesionandproliferationofepithelialcells AT sangeetakhare exvivohumancolontissueexposuretopristinegrapheneactivatesgenesinvolvedinthebindingadhesionandproliferationofepithelialcells
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Ex Vivo Human Colon Tissue Exposure to Pristine Graphene Activates Genes Involved in the Binding, Adhesion and Proliferation of Epithelial Cells

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