Fig. 6 | Signal Transduction and Targeted Therapy

Fig. 6

From: Cardiomyocyte-specific knockout of ADAM17 alleviates doxorubicin-induced cardiomyopathy via inhibiting TNFα–TRAF3–TAK1–MAPK axis

Fig. 6

Transcriptome profiles of the myocardium in four groups of mice and the relation between ADAM17 and TRAF3 in the regulation of apoptosis-associated proteins in the NRCMs. a KEGG pathway enrichment analysis of differential expressing (DE) transcripts and bubble chart showing KEGG pathways enrichment in the heart of A17fl/fl + NS and A17fl/fl + DOX mice. b Heat map of 26 genes, which showed significant difference in the TNF signaling pathway between A17fl/fl + NS and A17fl/fl + DOX mouse hearts, were compared between A17α-MHCKO + DOX and A17fl/fl + DOX mouse hearts and the differences between the latter two groups were ranked by p values with the smallest p value on the top. c Representative western blot images of TRAF3 expression in the myocardium of four groups of mice. d Comparison of TRAF3 expression among four groups of mice (n = 6 in each group). e, f Representative western blot images and comparison of TRAF3 expression in four groups of NRCMs treated with siNC + DMSO, siNC + DOX, siA17 + DMSO and siA17 + DOX, respectively (n = 6 in each group). g Representative western blot images of PARP, cleaved PARP, caspase 3 and cleaved caspase 3 expression among four groups of NRCMs treated with NC + DOX, oe17 + DOX, siTRAF3 + DOX and oeA17 + siTRAF3 + DOX, respectively. h Comparison of cleaved PARP/PARP expression among four groups of NRCMs treated with NC + DOX, oe17 + DOX, siTRAF3 + DOX and oeA17 + siTRAF3 + DOX, respectively (n = 6 in each group). i Comparison of cleaved caspase3/caspase3 expression among four groups of NRCMs treated with NC + DOX, oe17 + DOX, siTRAF3 + DOX and oeA17 + siTRAF3 + DOX, respectively (n = 6 in each group). j Serum levels of TNF-α in A17fl/fl and A17α-MHCKO mice treated with NS or DOX (n = 6 in each group). k Serum levels of TNF-α in AAV9-oeNC and AAV9-oeA17 mice treated with NS or DOX (n = 6 in each group). l Supernatant levels of TNF-α in four groups of NRCMs treated with siNC + DMSO, siNC + DOX, siA17 + DMSO and siA17 + DOX, respectively (n = 6 in each group). m Supernatant levels of TNF-α in four groups of NRCMs treated with NC + DMSO, NC + DOX, oeA17 + DMSO and oeA17 + DOX, respectively (n = 6 in each group). n, o Representative western blot images and comparison of TRAF3 protein expression in the NRCMs treated with TNF-α at different concentrations for 24 h (n = 6 in each group). p Comparison of TRAF3 mRNA expression in NRCMs treated with TNF-α at different concentrations for 24 h (n = 6 in each group). Values shown were mean and SEM. One-way ANOVA were applied in (d, f, hm, o and p). *p < 0.05; **p < 0.01; ***p < 0.001

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