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. 2017 Sep 1;31(17):1770–1783. doi: 10.1101/gad.305482.117

Figure 7.

Figure 7.

Anti-inflammatory drugs promote cardiac reprogramming. (A) 5F reprogrammed TTFs treated with either DMSO or the indicated anti-inflammatory drugs for 7 d after infection. Expression of inflammatory genes (IL6, Ccl2, and Ptgs1), and cardiac genes (Myh6, Actc1, and Nppa) was determined by qPCR. (Dex) 10 µM Dex; (Nab) 10 µM Nab. (B) Immunocytochemistry images of 5F reprogrammed adult αMHC-GFP transgenic TTFs treated with DMSO or the indicated anti-inflammatory drugs for 7 d. (Green) αMHC-GFP; (red) cTnT; (blue) Hoechst. Bars, 500 µm. (C,D) Representative flow cytometry plot (C) and analyses (D) of αMHC-GFP+ and cTnT+ cells in 5F reprogrammed adult αMHC-GFP transgenic TTFs treated with DMSO or the indicated anti-inflammatory drugs for 7 d. (*) P < 0.05. (E) Model showing the mechanism of action of ZNF281 on 5F-mediated direct cardiac reprogramming. ZNF281 is a cardiac transcription coactivator recruited by GATA4 to cardiac enhancers to activate cardiac gene expression. ZNF281 also represses the inflammatory response, which acts as a barrier pathway to cardiac reprogramming.