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

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

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13 Citations (Scopus)

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.

Original languageEnglish
Article number2163
JournalScientific Reports
Volume11
Issue number1
DOIs
Publication statusPublished - Dec 2021

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