| Texto completo | |
| Autor(es): |
Assis, Rahyza I. F.
[1]
;
Wiench, Malgorzata
[2]
;
Silverio, Karina G.
[1]
;
da Silva, Rodrigo A.
[3]
;
Feltran, Georgia da Silva
[3]
;
Sallum, Enilson A.
[1]
;
Casati, Marcio Z.
[1]
;
Nociti, Jr., Francisco H.
[1]
;
Andia, Denise C.
[1, 4]
Número total de Autores: 9
|
| Afiliação do(s) autor(es): | [1] Univ Estadual Campinas, Piracicaba Dent Sch, Dept Prosthodont & Periodont, Piracicaba, SP - Brazil
[2] Univ Birmingham, Sch Canc Sci, Sch Dent, Birmingham, W Midlands - England
[3] Sao Paulo State Univ, Biosci Inst, Dept Chem & Biochem, Botucatu, SP - Brazil
[4] Univ Paulista, Sch Dent, Div Epigenet, Hlth Sci Inst, Sao Paulo - Brazil
Número total de Afiliações: 4
|
| Tipo de documento: | Artigo Científico |
| Fonte: | PLoS One; v. 13, n. 12 DEC 3 2018. |
| Citações Web of Science: | 0 |
| Resumo | |
Human bone marrow-derived mesenchymal stem cells (hBMSCs) are important for tissue regeneration but their epigenetic regulation is not well understood. Here we investigate the ability of a non-nucleoside DNA methylation inhibitor, RG108 to induce epigenetic changes at both global and gene-specific levels in order to enhance mesenchymal cell markers, in hBMSCs. hBMSCs were treated with complete culture medium, 50 mu M RG108 and DMSO for three days and subjected to viability and apoptosis assays, global and gene-specific methylation/hydroxymethylation, transcript levels' analysis of epigenetic machinery enzymes and multipotency markers, protein activities of DNMTs and TETs, immunofluorescence staining and western blot analysis for NANOG and OCT4 and flow cytometry for CD105. The RG108, when used at 50 mu M, did not affect the viability, apoptosis and proliferation rates of hBMSCs or hydroxymethylation global levels while leading to 75% decrease in DNMTs activity and 42% loss of global DNA methylation levels. In addition, DNMT1 was significantly downregulated while TET1 was upregulated, potentially contributing to the substantial loss of methylation observed. Most importantly, the mesenchymal cell markers CD105, NANOG and OCT4 were upregulated being NANOG and OCT4 epigenetically modulated by RG108, at their gene promoters. We propose that RG108 could be used for epigenetic modulation, promoting epigenetic activation of NANOG and OCT4, without affecting the viability of hBMSCs. DMSO can be considered a modulator of epigenetic machinery enzymes, although with milder effect compared to RG108. (AU) | |
| Processo FAPESP: | 13/09650-8 - Regulação epigenética em células mesenquimais humanas |
| Beneficiário: | Denise Carleto Andia |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores |
| Processo FAPESP: | 15/02160-0 - Desmetilação de células mesenquimais indiferenciadas da medula óssea de humanos: regulação epigenética |
| Beneficiário: | Rahyza Inacio Freire de Assis |
| Modalidade de apoio: | Bolsas no Brasil - Mestrado |