Department of Structural and Functional Biology, Institute of Biology, University of Campinas (Unicamp), Campinas, SP, 13083-862, Brazil.
Epigenetics in Human Health and Disease Laboratory, Department of Diabetes, Central Clinical School, The Alfred Medical Research and Education Precinct, Monash University, Melbourne, VIC, Australia.
Sci Rep. 2021 Jan 25;11(1):2163. doi: 10.1038/s41598-021-81794-4.
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.
由于肝脏在代谢稳态和凝血因子及炎症固有免疫蛋白的分泌中起着重要作用，因此人们有兴趣了解高血糖状态下肝细胞激活的机制，以及这种激活是否可以通过药理学方法得到缓解。我们之前已经表明，高血糖刺激肝细胞染色质结构和代谢的重大变化，组蛋白去乙酰化酶抑制剂丙戊酸（VPA）能够逆转其中一些代谢变化。在这项研究中，我们使用 RNA 测序（RNA-seq）来研究 VPA 如何影响肝细胞中的基因表达。有趣的是，我们观察到 VPA 可减弱高血糖诱导的补体和凝血级联基因的激活。我们还观察到，许多基因激活事件与这些基因启动子处的组蛋白乙酰化变化同时发生，这表明表观遗传调控参与了 VPA 的作用。
