5-azacytidine과 DMSO 처리에 의한 성인 간엽성 줄기세포의 심근세포로의 분화과정에서 심근 조절인자들의 발현
(The) expression of cardiomyogenic regulatory factors during cardiomyogenic differentiation by 5-azacytidine and DMSO on human mesenchymal stem cell
5-azacytidine DMSO 간엽성 줄기세포;
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The limited ability of the heart to regenerate damaged tissue following a myocardial infarct results in loss of cardiac function, ventricular remodeling, and progressive dysfunction leading to congestive heart failure. A number of studies have suggested that the plasticity of adult stem cells is such that they can differentiate into cardiomyocytes. Therefore, there is a possibility of mesenchymal stem cell (MSC) for the therapy of heart failure. However, the study of cardiomyogenic differentiation of human mesenchymal stem cell ((h)_MSC) has been little reported. Also there are few reports regarding the expression of proteins that related to the cardiac myogenesis during cardiomyogenic differentiation. Therefore, this study was conducted to identify the effect of differentiation-induced agents (5-azacytidine and DMSO) for cardiomyogenic differentiation, and the mediated factors of differentiation agents during cardiomyogenic differentiation in the (h)_MSC. When treated with 5-azacytidine and DMSO of the (h)_MSC, the growth properties of the (h)_MSC were not obviously affected. And spontaneously beating cells were not found in the (h)_MSC. But the expression of Troponin-I and β-actin by the 5-azacytidien or DMSO treated (h)_MSC were detected. And cardiomyogenic transcription factors (GATA-4 and Nkx2.5) were expressed in 5-azacytidine and DMSO treated (h)_MSCs. These results suggest that (h)_MSC differentiate to cardiomyocyte by 5-azacytidine and DMSO treatment. When compared with differentiation-induced agents, Troponin-I and GATA4 of the DMSO treated group was more highly expressed than that of the 5-azacytidine treated group. Therefore DMSO treatment of (h)_MSC was more effective cardiomyogenic differentiation-induced agent. 5-azacytidine and DMSO directly affect transcription factor (GATA-4) expression. FGF-6 and IGF-I expression were time dependently increased, but FGF-2 and Wnts did not associated with cardiomyogenic differentiation. Therefore, these results suggest that (h)_MSC can be induced to differentiate in an expected cardiomyogenic lineage by 5-azacytidine and DMSO treatment. Moreover, 5-azacytidine and DMSO directly affect transcription factor (GATA-4) and FGF-6 expression. GATA-4 activates to the other cardiac transcription factor and growth factor. So (h)_MSC_(s) can be changed to the cardiomyogenic phenotype. The present study demonstrates the ability of adult (h)_MSC to undergo cardiomyogenic differentiation and opens the possibility for using these human adult stem cells for therapeutic cardiomyoplasty.