title: Initial pulmonary respiration causes massive diaphragm damage and hyper-CKemia in Duchenne muscular dystrophy dog.
abstract: The molecular mechanism of muscle degeneration in a lethal muscle disorder Duchene muscular dystrophy (DMD) has not been fully elucidated. The dystrophic dog, a model of DMD, shows a high mortality rate with a marked increase in serum creatine kinase (CK) levels in the neonatal period. By measuring serum CK levels in cord and venous blood, we found initial pulmonary respiration resulted in massive diaphragm damage in the neonates and thereby lead to the high serum CK levels. Furthermore, molecular biological techniques revealed that osteopontin was prominently upregulated in the dystrophic diaphragm prior to the respiration, and that immediate-early genes (c-fos and egr-1) and inflammation/immune response genes (IL-6, IL-8, COX-2, and selectin E) were distinctly overexpressed after the damage by the respiration. Hence, we segregated dystrophic phases at the molecular level before and after mechanical damage. These molecules could be biomarkers of muscle damage and potential targets in pharmaceutical therapies.
authors.affiliation: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Nakamura
authors.forename: Masanori
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Mutsuki
authors.initials: M
authors.lastname: Kuraoka
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Yuasa
authors.forename: Naoko
authors.initials: N
authors.lastname: Yugeta
authors.forename: Takashi
authors.initials: T
authors.lastname: Okada
authors.forename: Shin'ichi
authors.initials: S
authors.lastname: Takeda
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003402:Creatine Kinase / Q000097:blood*; D003964:Diaphragm / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004285:Dogs; D005786:Gene Expression Regulation; D006818:Hyalin / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D058977:Molecular Sequence Annotation; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D059748:Proteolysis; D012119:Respiration / Q000235:genetics; D015398:Signal Transduction; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D053495:Osteopontin; D003402:Creatine Kinase