Inhibition of DNA methylation enhances HLA-G expression in human mesenchymal stem cells
| Autor: | Takele Teklemariam, Longmei Zhao, Basil M. Hantash, Bhamini Purandare |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
medicine.drug_class
Primary Cell Culture Biophysics Adipose tissue Bone Marrow Cells Biology Decitabine Biochemistry Epigenesis Genetic chemistry.chemical_compound Downregulation and upregulation medicine Humans RNA Messenger Epigenetics Molecular Biology HLA-G Antigens Reverse Transcriptase Polymerase Chain Reaction Valproic Acid Mesenchymal stem cell Histone deacetylase inhibitor Mesenchymal Stem Cells Cell Biology DNA Methylation Molecular biology Demethylating agent medicine.anatomical_structure Adipose Tissue chemistry DNA methylation Azacitidine Cancer research Bone marrow Signal Transduction |
| Zdroj: | Biochemical and Biophysical Research Communications. 452:753-759 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2014.08.152 |
| Popis: | Mesenchymal stem cells (MSCs) are immunosuppressive multipotent cells under investigation for potential therapeutic applications in regenerative medicine and prevention of graft-versus-host disease. Human leukocyte antigen (HLA)-G contributes to the immunomodulatory properties of MSCs. HLA-G expression in MSCs is very low and diminishes during in vitro expansion. Epigenetic regulation activates HLA-G expression in some cancer cell lines but not in MSCs. In the present study, adipose- and bone marrow-derived MSCs were exposed to the DNA demethylating agent 5-aza-2-deoxycytidine (5-aza-dC) and histone deacetylase inhibitor valproic acid (VPA) and HLA-G mRNA levels assessed using semi-quantitative reverse-transcription PCR. Exposure to 5-aza-dC resulted in HLA-G1 and -G3 upregulation in both early and late passage MSCs. VPA treatment did not induce HLA-G expression in both bone marrow and adipose derived MSCs. Our results provide the first evidence that HLA-G3 could be expressed in MSCs and that methylation-mediated repression is partly responsible for the observed low levels of HLA-G expression in MSCs. Our findings provide insight that treatment of MSCs with specific epigenetic regulatory modulators may improve their immunoregulatory capability for therapeutic applications. |
| Databáze: | OpenAIRE |
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