Inhibition of profibrotic signalling enhances the 5-azacytidine-induced reprogramming of fibroblasts into cardiomyocytes.

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. PMID: 32114121 [PubMed - as supplied by publisher]
Source: The International Journal of Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Int J Biochem Cell Biol Source Type: research