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5-azacytidine promotes terminal differentiation of hepatic progenitor cells
- Source :
- Molecular medicine reports. 12(2)
- Publication Year :
- 2014
-
Abstract
- 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 5-azaC 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 5-azaC at concentrations from 0 to 20 μmol/l, in addition to hepatocyte induction culture medium. Hepatocyte induction medium induces HP14.5 cell differentiation. 5-azaC may enhance the albumin promotor-driven Gaussia luciferase (ALB-GLuc) 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 hepatocyte-associated factors was not significantly different between the group treated with 5-azaC 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 5-azaC, were higher than those in the induced group without 5-azaC, although no significant differences were detected in expression of the hepatic stem cell markers, DLK and α-fetoprotein, between the two groups. Treatment with 5-azaC alone did not affect glycogen synthesis or indocyanine green (ICG) metabolic function in HP14.5 cells, although it significantly increased ICG uptake and periodic acid-Schiff-positive cell numbers amongst HP14.5 cells. Therefore, the present study demonstrated that treatment with 5-azaC alone exerted no effects on the maturation and differentiation of HP14.5 cells. However, 5-azaC exhibited a synergistic effect on the terminal differentiation of induced hepatic progenitor cells in association with a hepatic induction medium.
- Subjects :
- Cancer Research
Cellular differentiation
Biology
Biochemistry
Mice
Tyrosine aminotransferase
Genetics
medicine
Cytochrome P-450 CYP1A1
Animals
RNA, Messenger
Progenitor cell
Glucuronosyltransferase
Molecular Biology
Cells, Cultured
Tyrosine Transaminase
Hepatocyte differentiation
Keratin-18
Stem Cells
Calcium-Binding Proteins
Cell Differentiation
Cell cycle
Embryo, Mammalian
Molecular biology
Embryonic stem cell
medicine.anatomical_structure
Oncology
Apoptosis
Hepatocyte
Azacitidine
Hepatocytes
Molecular Medicine
Intercellular Signaling Peptides and Proteins
alpha-Fetoproteins
Subjects
Details
- ISSN :
- 17913004
- Volume :
- 12
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Molecular medicine reports
- Accession number :
- edsair.doi.dedup.....d54d32eaf154fbb80cf9cdab45cdbcbc