| First Author | Peterson JM | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 3431 |
| PubMed ID | 30143619 | Mgi Jnum | J:266248 |
| Mgi Id | MGI:6209020 | Doi | 10.1038/s41467-018-05910-1 |
| Citation | Peterson JM, et al. (2018) NF-kappaB inhibition rescues cardiac function by remodeling calcium genes in a Duchenne muscular dystrophy model. Nat Commun 9(1):3431 |
| abstractText | Duchenne muscular dystrophy (DMD) is a neuromuscular disorder causing progressive muscle degeneration. Although cardiomyopathy is a leading mortality cause in DMD patients, the mechanisms underlying heart failure are not well understood. Previously, we showed that NF-kappaB exacerbates DMD skeletal muscle pathology by promoting inflammation and impairing new muscle growth. Here, we show that NF-kappaB is activated in murine dystrophic (mdx) hearts, and that cardiomyocyte ablation of NF-kappaB rescues cardiac function. This physiological improvement is associated with a signature of upregulated calcium genes, coinciding with global enrichment of permissive H3K27 acetylation chromatin marks and depletion of the transcriptional repressors CCCTC-binding factor, SIN3 transcription regulator family member A, and histone deacetylase 1. In this respect, in DMD hearts, NF-kappaB acts differently from its established role as a transcriptional activator, instead promoting global changes in the chromatin landscape to regulate calcium genes and cardiac function. |
