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.