title: Identification of muscle-specific microRNAs in serum of muscular dystrophy animal models: promising novel blood-based markers for muscular dystrophy.
abstract: Duchenne muscular dystrophy (DMD) is a lethal X-linked disorder caused by mutations in the dystrophin gene, which encodes a cytoskeletal protein, dystrophin. Creatine kinase (CK) is generally used as a blood-based biomarker for muscular disease including DMD, but it is not always reliable since it is easily affected by stress to the body, such as exercise. Therefore, more reliable biomarkers of muscular dystrophy have long been desired. MicroRNAs (miRNAs) are small, ∼22 nucleotide, noncoding RNAs which play important roles in the regulation of gene expression at the post-transcriptional level. Recently, it has been reported that miRNAs exist in blood. In this study, we hypothesized that the expression levels of specific serum circulating miRNAs may be useful to monitor the pathological progression of muscular diseases, and therefore explored the possibility of these miRNAs as new biomarkers for muscular diseases. To confirm this hypothesis, we quantified the expression levels of miRNAs in serum of the dystrophin-deficient muscular dystrophy mouse model, mdx, and the canine X-linked muscular dystrophy in Japan dog model (CXMD(J)), by real-time PCR. We found that the serum levels of several muscle-specific miRNAs (miR-1, miR-133a and miR-206) are increased in both mdx and CXMD(J). Interestingly, unlike CK levels, expression levels of these miRNAs in mdx serum are little influenced by exercise using treadmill. These results suggest that serum miRNAs are useful and reliable biomarkers for muscular dystrophy.
authors.affiliation: Administrative Section of Radiation Protection, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
authors.forename: Hideya
authors.initials: H
authors.lastname: Mizuno
authors.forename: Akinori
authors.initials: A
authors.lastname: Nakamura
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Aoki
authors.forename: Naoki
authors.initials: N
authors.lastname: Ito
authors.forename: Soichiro
authors.initials: S
authors.lastname: Kishi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sekiguchi
authors.forename: Shin'ichi
authors.initials: S
authors.lastname: Takeda
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hashido
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D004285:Dogs; D051379:Mice; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D009132:Muscles / Q000473:pathology*; D009136:Muscular Dystrophies / Q000097:blood* / Q000235:genetics*; D009137:Muscular Dystrophy, Animal / Q000097:blood* / Q000235:genetics*; D009928:Organ Specificity / Q000235:genetics
chemical_list: D015415:Biomarkers; D035683:MicroRNAs