Translating golden retriever muscular dystrophy microarray findings to novel biomarkers for cardiac/skeletal muscle function in Duchenne muscular dystrophy. Pediatr Res 2016 Apr;79(4):629-36
Date
12/18/2015Pubmed ID
26672735Pubmed Central ID
PMC4837049DOI
10.1038/pr.2015.257Scopus ID
2-s2.0-84964403684 (requires institutional sign-in at Scopus site) 23 CitationsAbstract
BACKGROUND: In Duchenne muscular dystrophy (DMD), abnormal cardiac function is typically preceded by a decade of skeletal muscle disease. Molecular reasons for differences in onset and progression of these muscle groups are unknown. Human biomarkers are lacking.
METHODS: We analyzed cardiac and skeletal muscle microarrays from normal and golden retriever muscular dystrophy (GRMD) dogs (ages 6, 12, or 47+ mo) to gain insight into muscle dysfunction and to identify putative DMD biomarkers. These biomarkers were then measured using human DMD blood samples.
RESULTS: We identified GRMD candidate genes that might contribute to the disparity between cardiac and skeletal muscle disease, focusing on brain-derived neurotropic factor (BDNF) and osteopontin (OPN/SPP1, hereafter indicated as SPP1). BDNF was elevated in cardiac muscle of younger GRMD but was unaltered in skeletal muscle, while SPP1 was increased only in GRMD skeletal muscle. In human DMD, circulating levels of BDNF were inversely correlated with ventricular function and fibrosis, while SPP1 levels correlated with skeletal muscle function.
CONCLUSION: These results highlight gene expression patterns that could account for differences in cardiac and skeletal disease in GRMD. Most notably, animal model-derived data were translated to DMD and support use of BDNF and SPP1 as biomarkers for cardiac and skeletal muscle involvement, respectively.
Author List
Galindo CL, Soslow JH, Brinkmeyer-Langford CL, Gupte M, Smith HM, Sengsayadeth S, Sawyer DB, Benson DW, Kornegay JN, Markham LWMESH terms used to index this publication - Major topics in bold
AnimalsBiomarkers
Case-Control Studies
Cohort Studies
Dogs
Heart
Humans
Muscle, Skeletal
Muscular Dystrophy, Duchenne
Oligonucleotide Array Sequence Analysis