title: Valproic Acid Increases the Hepatic Differentiation Potential of Salivary Gland Cells.
abstract: The studies of cell plasticity and differentiation abilities are important problems in modern cellular biology. The use of histone deacetylase inhibitor - valproic acid is a promising approach to increasing the differentiation efficiency of various cell types. In this paper we investigate the ability of mouse submandibular salivary gland cells to differentiate into the hepatic direction and the effect of valproic acid on the efficiency of this differentiation. It was shown that the gene expression levels of hepatocyte markers (Aat, Afp, G6p, Pepck, Tat, Cyp3a13) and liver-enriched transcription factors (Hnf-3α, Hnf-3β, Hnf-4α, Hnf-6) were increased after differentiation in salivary gland cells. Valproic acid increases the specificity of hepatic differentiation, reducing the expression levels of the ductal (Krt19, Hhex1, Cyp7a1) and acinar (Ptf1a) markers. After valproic acid exposure, the efficiency of hepatic differentiation also increases, as evidenced by the increase in the gene expression level of Alb and Tdo, and increase in urea production by differentiated cells. No change was found in DNA methylation of the promoter regions of the genes; however, valproic acid treatment and subsequent hepatic differentiation largely affected the histone H3 methylation of liver-enriched genes. Thus, mouse submandibular salivary gland cells are capable of effective differentiation in the hepatic direction. Valproic acid increases the specificity and efficiency of the hepatic differentiation of these cells.
authors.affiliation: Lomonosov Moscow State University, Faculty of Biology, Leninskie Gory, Moscow State University, 1, bld. 12, 119991, Moscow, Russia ; Pirogov Russian National Research Medical University, Ostrovitianov str., 1, 117997, Moscow, Russia ; Koltsov Institute of Developmental Biology, Russian Academy of Sciences, Vavilova str., 26, 119334 , Moscow, Russia.
authors.forename: O S
authors.initials: OS
authors.lastname: Petrakova
authors.affiliation: Belozersky Institute, Moscow State University, Leninskie Gory, 1/40, 119991, Moscow, Russia.
authors.forename: V V
authors.initials: VV
authors.lastname: Ashapkin
authors.affiliation: Department of bioengineering and bioinformatics, Lomonosov Moscow State University, Leninskie Gory, 1/73, 119991, Moscow, Russia.
authors.forename: V Y
authors.initials: VY
authors.lastname: Shtratnikova
authors.affiliation: Belozersky Institute, Moscow State University, Leninskie Gory, 1/40, 119991, Moscow, Russia.
authors.forename: L I
authors.initials: LI
authors.lastname: Kutueva
authors.affiliation: Lomonosov Moscow State University, Faculty of Biology, Leninskie Gory, Moscow State University, 1, bld. 12, 119991, Moscow, Russia ; Pirogov Russian National Research Medical University, Ostrovitianov str., 1, 117997, Moscow, Russia ; Koltsov Institute of Developmental Biology, Russian Academy of Sciences, Vavilova str., 26, 119334 , Moscow, Russia.
authors.forename: E A
authors.initials: EA
authors.lastname: Vorotelyak
authors.affiliation: Pirogov Russian National Research Medical University, Ostrovitianov str., 1, 117997, Moscow, Russia.
authors.forename: M A
authors.initials: MA
authors.lastname: Borisov
authors.affiliation: Koltsov Institute of Developmental Biology, Russian Academy of Sciences, Vavilova str., 26, 119334 , Moscow, Russia.
authors.forename: V V
authors.initials: VV
authors.lastname: Terskikh
authors.affiliation: Pirogov Russian National Research Medical University, Ostrovitianov str., 1, 117997, Moscow, Russia ; Koltsov Institute of Developmental Biology, Russian Academy of Sciences, Vavilova str., 26, 119334 , Moscow, Russia.
authors.forename: I G
authors.initials: IG
authors.lastname: Gvazava
authors.affiliation: Koltsov Institute of Developmental Biology, Russian Academy of Sciences, Vavilova str., 26, 119334 , Moscow, Russia.
authors.forename: A V
authors.initials: AV
authors.lastname: Vasiliev
keywords: gene expression; hepatic differentiation; submandibular salivary gland cells; valproic acid