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5-azacytidine promotes terminal differentiation of hepatic progenitor cells

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5-azacytidine (5-azaC) is known to induce cardiomyocyte differentiation. However, its function in hepatocyte differentiation is unclear. The present study investigated the in vitro capability of 5azaC to promote maturation and differentiation of mouse embryonic hepatic progenitor cells, with the aim of developing an approach for improving hepatic differentiation. Mouse embryonic hepatic progenitor cells (HP14.5 cells) were treated with 5azaC at concentrations from 0 to 20 µmol/l, in addition to hepatocyte induction culture medium. Hepatocyte induction medium induces HP14.5 cell differentiation. 5azaC may enhance the albumin promotordriven Gaussia luciferase (ALBGLuc) activity in induced HP14.5 cells. In the present study 2 µmol/l was found to be the optimum concentration with which to achieve this. The expression of hepatocyteassociated factors was not significantly different between the group treated with 5azaC alone and the control group. The mRNA levels of ALB; cytokeratin 18 (CK18); tyrosine aminotransferase (TAT); and cytochrome p450, family 1, member A1 (CYP1A1); in addition to the protein levels of ALB, CK18 and uridine diphosphate glucuronyltransferase 1A (UGT1A) in the induced group with 5azaC, were higher than those in the induced group without 5azaC, although no significant differences were detected in expression of the hepatic stem cell markers, DLK and αfetoprotein, between the two groups. Treatment with 5azaC alone did not affect glycogen synthesis or indocyanine green (ICG) metabolic function in HP14.5 cells, although it significantly increased ICG uptake and periodic acidSchiffpositive cell numbers amongst HP14.5 cells. Therefore, the present study demonstrated that treatment with 5azaC alone exerted no effects on the maturation and differentiation of HP14.5 cells. However, 5azaC exhibited a synergistic effect on the terminal differentiation of induced hepatic progenitor cells in association with a hepatic induction medium.
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Document Type: Research Article

Affiliations: 1: Department of Pediatric Surgery, The Children's Hospital of Chongqing Medical University, Chongqing 400014, P.R. China 2: Stem Cell Biology and Therapy Laboratory, The Children's Hospital of Chongqing Medical University, Chongqing 400014, P.R. China

Publication date: August 1, 2015

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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