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Translating golden retriever muscular dystrophy microarray findings to novel biomarkers for cardiac/skeletal muscle function in Duchenne muscular dystrophy
- Source :
- Pediatric research
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
Abstract
- 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+ months) 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). 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.
- Subjects :
- musculoskeletal diseases
0301 basic medicine
Golden retriever muscular dystrophy
Validation study
Pathology
medicine.medical_specialty
Microarray
Duchenne muscular dystrophy
030204 cardiovascular system & hematology
Article
Cohort Studies
03 medical and health sciences
Dogs
0302 clinical medicine
medicine
Animals
Humans
Muscular dystrophy
Muscle, Skeletal
Oligonucleotide Array Sequence Analysis
Extramural
business.industry
Skeletal muscle
Heart
medicine.disease
Muscular Dystrophy, Duchenne
030104 developmental biology
medicine.anatomical_structure
Case-Control Studies
Pediatrics, Perinatology and Child Health
business
Biomarkers
Subjects
Details
- ISSN :
- 15300447 and 00313998
- Volume :
- 79
- Database :
- OpenAIRE
- Journal :
- Pediatric Research
- Accession number :
- edsair.doi.dedup.....261672a98943e8fd386f335c25a03918