Valproic acid influences the expression of genes implicated with hyperglycaemia-induced complement and coagulation pathways

Abstract Because the liver plays a major role in metabolic homeostasis and secretion of clotting factors and inflammatory innate immune proteins, there is interest in understanding the mechanisms of hepatic cell activation under hyperglycaemia and whether this can be attenuated pharmacologically. We...

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Autores principales:	Marina Barreto Felisbino, Mark Ziemann, Ishant Khurana, Jun Okabe, Keith Al-Hasani, Scott Maxwell, K. N. Harikrishnan, Camila Borges Martins de Oliveira, Maria Luiza S. Mello, Assam El-Osta
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/003e0b1330af43baa6106c9dd0f31214
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spelling	oai:doaj.org-article:003e0b1330af43baa6106c9dd0f312142021-12-02T10:48:02ZValproic acid influences the expression of genes implicated with hyperglycaemia-induced complement and coagulation pathways10.1038/s41598-021-81794-42045-2322https://doaj.org/article/003e0b1330af43baa6106c9dd0f312142021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81794-4https://doaj.org/toc/2045-2322Abstract Because the liver plays a major role in metabolic homeostasis and secretion of clotting factors and inflammatory innate immune proteins, there is interest in understanding the mechanisms of hepatic cell activation under hyperglycaemia and whether this can be attenuated pharmacologically. We have previously shown that hyperglycaemia stimulates major changes in chromatin organization and metabolism in hepatocytes, and that the histone deacetylase inhibitor valproic acid (VPA) is able to reverse some of these metabolic changes. In this study, we have used RNA-sequencing (RNA-seq) to investigate how VPA influences gene expression in hepatocytes. Interesting, we observed that VPA attenuates hyperglycaemia-induced activation of complement and coagulation cascade genes. We also observe that many of the gene activation events coincide with changes to histone acetylation at the promoter of these genes indicating that epigenetic regulation is involved in VPA action.Marina Barreto FelisbinoMark ZiemannIshant KhuranaJun OkabeKeith Al-HasaniScott MaxwellK. N. HarikrishnanCamila Borges Martins de OliveiraMaria Luiza S. MelloAssam El-OstaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marina Barreto Felisbino Mark Ziemann Ishant Khurana Jun Okabe Keith Al-Hasani Scott Maxwell K. N. Harikrishnan Camila Borges Martins de Oliveira Maria Luiza S. Mello Assam El-Osta Valproic acid influences the expression of genes implicated with hyperglycaemia-induced complement and coagulation pathways
description	Abstract Because the liver plays a major role in metabolic homeostasis and secretion of clotting factors and inflammatory innate immune proteins, there is interest in understanding the mechanisms of hepatic cell activation under hyperglycaemia and whether this can be attenuated pharmacologically. We have previously shown that hyperglycaemia stimulates major changes in chromatin organization and metabolism in hepatocytes, and that the histone deacetylase inhibitor valproic acid (VPA) is able to reverse some of these metabolic changes. In this study, we have used RNA-sequencing (RNA-seq) to investigate how VPA influences gene expression in hepatocytes. Interesting, we observed that VPA attenuates hyperglycaemia-induced activation of complement and coagulation cascade genes. We also observe that many of the gene activation events coincide with changes to histone acetylation at the promoter of these genes indicating that epigenetic regulation is involved in VPA action.
format	article
author	Marina Barreto Felisbino Mark Ziemann Ishant Khurana Jun Okabe Keith Al-Hasani Scott Maxwell K. N. Harikrishnan Camila Borges Martins de Oliveira Maria Luiza S. Mello Assam El-Osta
author_facet	Marina Barreto Felisbino Mark Ziemann Ishant Khurana Jun Okabe Keith Al-Hasani Scott Maxwell K. N. Harikrishnan Camila Borges Martins de Oliveira Maria Luiza S. Mello Assam El-Osta
author_sort	Marina Barreto Felisbino
title	Valproic acid influences the expression of genes implicated with hyperglycaemia-induced complement and coagulation pathways
title_short	Valproic acid influences the expression of genes implicated with hyperglycaemia-induced complement and coagulation pathways
title_full	Valproic acid influences the expression of genes implicated with hyperglycaemia-induced complement and coagulation pathways
title_fullStr	Valproic acid influences the expression of genes implicated with hyperglycaemia-induced complement and coagulation pathways
title_full_unstemmed	Valproic acid influences the expression of genes implicated with hyperglycaemia-induced complement and coagulation pathways
title_sort	valproic acid influences the expression of genes implicated with hyperglycaemia-induced complement and coagulation pathways
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/003e0b1330af43baa6106c9dd0f31214
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Valproic acid influences the expression of genes implicated with hyperglycaemia-induced complement and coagulation pathways

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