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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doaj-003e0b1330af43baa6106c9dd0f312142021-01-31T16:21:00ZengNature Publishing GroupScientific Reports2045-23222021-01-0111111210.1038/s41598-021-81794-4Valproic acid influences the expression of genes implicated with hyperglycaemia-induced complement and coagulation pathwaysMarina Barreto Felisbino0Mark Ziemann1Ishant Khurana2Jun Okabe3Keith Al-Hasani4Scott Maxwell5K. N. Harikrishnan6Camila Borges Martins de Oliveira7Maria Luiza S. Mello8Assam El-Osta9Department of Structural and Functional Biology, Institute of Biology, University of Campinas (Unicamp)Epigenetics in Human Health and Disease Laboratory, Department of Diabetes, Central Clinical School, The Alfred Medical Research and Education Precinct, Monash UniversityEpigenetics in Human Health and Disease Laboratory, Department of Diabetes, Central Clinical School, The Alfred Medical Research and Education Precinct, Monash UniversityEpigenetics in Human Health and Disease Laboratory, Department of Diabetes, Central Clinical School, The Alfred Medical Research and Education Precinct, Monash UniversityEpigenetics in Human Health and Disease Laboratory, Department of Diabetes, Central Clinical School, The Alfred Medical Research and Education Precinct, Monash UniversityEpigenetics in Human Health and Disease Laboratory, Department of Diabetes, Central Clinical School, The Alfred Medical Research and Education Precinct, Monash UniversityEpigenetics in Human Health and Disease Laboratory, Department of Diabetes, Central Clinical School, The Alfred Medical Research and Education Precinct, Monash UniversityDepartment of Structural and Functional Biology, Institute of Biology, University of Campinas (Unicamp)Department of Structural and Functional Biology, Institute of Biology, University of Campinas (Unicamp)Epigenetics in Human Health and Disease Laboratory, Department of Diabetes, Central Clinical School, The Alfred Medical Research and Education Precinct, Monash UniversityAbstract 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.https://doi.org/10.1038/s41598-021-81794-4 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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 |
spellingShingle |
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 Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-01-01 |
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. |
url |
https://doi.org/10.1038/s41598-021-81794-4 |
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