NF-κB inhibition rescues cardiac function by remodeling calcium genes in a Duchenne muscular dystrophy model
Year: 2018
Type: article
Abstract: 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-κB exacerbates DMD skeletal muscle pathology by promoting inflammation and impairing new muscle growth. Here, we show that NF-κB is activated in murine dystrophic (mdx) hearts, and that cardiomyocyte ablation of NF-κB 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-κB 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.
Source: Nature Communications
Authors: Jennifer M. Peterson, David J. Wang, Vikram Shettigar, Steve R. Roof, Benjamin D. Canan, Nadine Bakkar, Jonathan Shintaku, Jin-Mo Gu, Sean C. Little, Nivedita M. Ratnam, Priya Londhe, Leina Lu, Christopher E. Gaw, Jennifer M. Petrosino, Sandya Liyanarachchi, Huating Wang, Paul M. L. Janssen, Jonathan P. Davis, Mark T. Ziolo, Sudarshana M. Sharma, Denis C. Guttridge
Institutions: Binghamton University, The Ohio State University Wexner Medical Center, Center for Muscle Health and Neuromuscular Disorders, The Ohio State University, Medical University of South Carolina, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Columbia University Irving Medical Center, Emory University, Bristol-Myers Squibb (United States), Tufts Medical Center, Chinese University of Hong Kong, Case Western Reserve University, Children's Hospital of Philadelphia
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Muscular Dystrophy Association, Parent Project Muscular Dystrophy, Ohio State University, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases
OpenAlex ID: W2888719982