Recent studies have shown that cardiac fibroblasts (CFs) can be transformed into induced cardiomyocytes (iCMs). This phenomenon represents a potential method for rescuing damaged myocardia after myocardial infarction. The mechanism underlying cardiac reprogramming regulation must be clarified to improve the induction efficiency of iCMs. In this study, we treated CFs with 5-aza for 24 h and added TGF-β inhibitor A83-01 for 2 weeks in vitro to investigate the effect of inhibiting fibrosis on myocardial differentiation. Inhibition of TGF-β1 activity with A83-01 significantly decreased the expressions of collagen III and α-SMA and increased the expression of myocardial specific marker cTnT and gap junction protein Cx43 in CFs, enhanced cardiac reprogramming as opposed to 2 weeks with 5-aza alone. Transcriptome and quantitative real-time reverse transcription-polymerase chain reaction analysis at the 14th day postinduction of A83-01 revealed that the expression of genes involved in cardiac development increased in the presence of 5-aza. These findings suggest that the addition of A83-01 remarkably inhibits profibrotic signalling and improved the efficiency of iCMs, provide new insights into the molecular mechanisms of cardiac reprogramming and promote the use of iCMs in clinical applications.

最近的研究表明，心脏成纤维细胞（CFs）可以转化为诱导的心肌细胞（iCMs）。此现象代表抢救心肌梗死后受损心肌的一种潜在方法。必须阐明心脏重编程调节的机制，以提高iCM的诱导效率。在这项研究中，我们在体外用5-氮杂（aza）处理CFs 24小时，并在体外添加TGF-β抑制剂A83-01 2周，以研究抑制纤维化对心肌分化的影响。用A83-01抑制TGF-β1活性可显着降低CF中胶原III和α-SMA的表达，并增加心肌特异性标志物cTnT和间隙连接蛋白Cx43的表达，从而增强了心脏重编程，而使用5-氮杂2周单独。A83-01诱导后第14天的转录组和实时定量逆转录聚合酶链反应分析表明，存在5-氮杂时，参与心脏发育的基因表达增加。这些发现表明，A83-01的添加显着抑制了纤维化信号传导并提高了iCM的效率，为心脏重编程的分子机制提供了新见识，并促进了iCM在临床应用中的使用。