雷帕霉素诱导Mef2c表达促进心肌分化

Rapamycin facilitates cardiac differentiation via upregulating Mef2c

目的:评价小分子化合物雷帕霉素、羟氯喹和MC1568对心肌分化效率和心肌分化转录因子Mef2c表达的影响。方法:利用DMSO诱导P19CL6小鼠畸胎瘤干细胞分化为自发跳动的心肌细胞,检测自噬诱导剂雷帕霉素对小鼠P19CL6畸胎瘤细胞向心肌分化的影响,研究相关机制。结果:自噬诱导剂雷帕霉素能够有效促进心肌分化,增强心肌标志性基因表达;自噬抑制剂羟氯喹能抑制DMSO诱导的P19CL6细胞心肌分化。雷帕霉素促进心肌分化转录因子Mef2c表达;采用Mef2c的小分子抑制剂MC1568,则能抑制雷帕霉素诱导的心肌早期和晚期分化标志基因表达。结论:雷帕霉素诱导的Mef2c表达是增强心肌分化能力所必需的。

Objective:To evaluat the effects of small molecular compounds rapamycin,hydroxychloroquine,and MC1568 on myocardial differentiation and Mef2c expression.Methods:DMSO was used to induce P19CL6 mouse teratoma stem cells to differentiate into spontaneously beating cardiomyocytes.The effect of autophagy inducer rapamycin on the differentiation of P19CL6 mouse teratoma cells into myocardium was detected,and the related mechanism was studied.Results:That rapamycin,an inducer of autophagy,could effectively promote myocardial differentiation and enhance the expression of myocardial marker genes.In contrast,the autophagy inhibitor hydroxychloroquine attenuated DMSO-induced myocardial differentiation in P19CL6 cells.That rapamycin promoted the expression of Mef2c,a myocardial differentiation transcription factor.However,a Mef2c small molecule inhibitor,MC1568,inhibited rapamycin-enhanced cardiac differentiation,downregulating the expression of early-and late-stage cardiac differentiation marker genes.Conclusion:This result indicated that rapamycin-induced Mef2c expression is necessary to enhanced m yocardial differentiation.