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

Autor(es)

Felisbino, Marina Barreto ^{[1, 2]} ; Ziemann, Mark ^[2] ; Khurana, Ishant ^[2] ; Okabe, Jun ^[2] ; Al-Hasani, Keith ^[2] ; Maxwell, Scott ^[2] ; Harikrishnan, K. N. ^[2] ; Martins de Oliveira, Camila Borges ^[1] ; Mello, Maria Luiza S. ^[1] ; El-Osta, Assam ^{[2, 3, 4, 5, 6]}

Afiliação do(s) autor(es)

^[1] Univ Campinas Unicamp, Inst Biol, Dept Struct & Funct Biol, BR-13083862 Campinas, SP - Brazil

^[2] Monash Univ, Cent Clin Sch, Dept Diabet, Alfred Med Res & Educ Precinct, Epigenet Human Hlth & Dis Lab, Melbourne, Vic - Australia

^[3] Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong - Peoples R China

^[4] Chinese Univ Hong Kong, Prince Wales Hosp, Hong Kong Inst Diabet & Obes, 3-F Lui Che Woo Clin Sci Bldg, 30-32 Ngan Shing St, Hong Kong - Peoples R China

^[5] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong - Peoples R China

^[6] Univ Coll Copenhagen, Fac Hlth, Dept Technol, Biomed Lab Sci, Copenhagen - Denmark

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 11, n. 1 JAN 25 2021.
• Citações Web of Science: 2

Resumo

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. (AU)

• Processo FAPESP: 14/10198-5 - Análise global do genoma (genome-wide) de células HepG2 tratadas com VPA sob condições de hiperglicemia
• Beneficiário: Marina Barreto Felisbino
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 10/50015-6 - Estrutura e organização da cromatina com o envelhecimento e o diabetes frente a alterações induzidas em marcadores epigenéticos
• Beneficiário: Maria Luiza Silveira Mello
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/10356-2 - Atuação do ácido valproico ao nível estrutural e funcional da cromatina
• Beneficiário: Maria Luiza Silveira Mello
• Modalidade de apoio: Auxílio à Pesquisa - Temático