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Laminin α2 Chain-Deficiency is Associated with microRNA Deregulation in Skeletal Muscle and Plasma.

Holmberg, Johan K LU ; Alajbegovic, Azra LU ; Gawlik, Kinga LU ; Elowsson, Linda LU and Durbeej-Hjalt, Madeleine LU (2014) In Frontiers in Aging Neuroscience 6(Jul 3).
Abstract
microRNAs (miRNAs) are widespread regulators of gene expression, but little is known of their potential roles in congenital muscular dystrophy type 1A (MDC1A). MDC1A is a severe form of muscular dystrophy caused by mutations in the gene encoding laminin α2 chain. To gain insight into the pathophysiological roles of miRNAs associated with MDC1A pathology, laminin α2 chain-deficient mice were evaluated by quantitative PCR. We demonstrate that expression of muscle-specific miR-1, miR-133a, and miR-206 is deregulated in laminin α2 chain-deficient muscle. Furthermore, expression of miR-223 and miR-21, associated with immune cell infiltration and fibrosis, respectively, is altered. Finally, we show that plasma levels of muscle-specific miRNAs... (More)
microRNAs (miRNAs) are widespread regulators of gene expression, but little is known of their potential roles in congenital muscular dystrophy type 1A (MDC1A). MDC1A is a severe form of muscular dystrophy caused by mutations in the gene encoding laminin α2 chain. To gain insight into the pathophysiological roles of miRNAs associated with MDC1A pathology, laminin α2 chain-deficient mice were evaluated by quantitative PCR. We demonstrate that expression of muscle-specific miR-1, miR-133a, and miR-206 is deregulated in laminin α2 chain-deficient muscle. Furthermore, expression of miR-223 and miR-21, associated with immune cell infiltration and fibrosis, respectively, is altered. Finally, we show that plasma levels of muscle-specific miRNAs are markedly elevated in laminin α2 chain-deficient mice and partially normalized in response to proteasome inhibition therapy. Altogether, our data suggest important roles for miRNAs in MDC1A pathology and we propose plasma levels of muscle-specific miRNAs as promising biomarkers for the progression of MDC1A. (Less)
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organization
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Contribution to journal
publication status
published
subject
in
Frontiers in Aging Neuroscience
volume
6
issue
Jul 3
publisher
Frontiers
external identifiers
  • pmid:25071564
  • wos:000339638100001
  • scopus:84904687690
ISSN
1663-4365
DOI
10.3389/fnagi.2014.00155
language
English
LU publication?
yes
id
b273a3b0-afc6-4b7d-99bb-5189a6b32d66 (old id 4581102)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25071564?dopt=Abstract
date added to LUP
2014-08-09 18:25:27
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2017-10-01 04:24:33
@article{b273a3b0-afc6-4b7d-99bb-5189a6b32d66,
  abstract     = {microRNAs (miRNAs) are widespread regulators of gene expression, but little is known of their potential roles in congenital muscular dystrophy type 1A (MDC1A). MDC1A is a severe form of muscular dystrophy caused by mutations in the gene encoding laminin α2 chain. To gain insight into the pathophysiological roles of miRNAs associated with MDC1A pathology, laminin α2 chain-deficient mice were evaluated by quantitative PCR. We demonstrate that expression of muscle-specific miR-1, miR-133a, and miR-206 is deregulated in laminin α2 chain-deficient muscle. Furthermore, expression of miR-223 and miR-21, associated with immune cell infiltration and fibrosis, respectively, is altered. Finally, we show that plasma levels of muscle-specific miRNAs are markedly elevated in laminin α2 chain-deficient mice and partially normalized in response to proteasome inhibition therapy. Altogether, our data suggest important roles for miRNAs in MDC1A pathology and we propose plasma levels of muscle-specific miRNAs as promising biomarkers for the progression of MDC1A.},
  articleno    = {155},
  author       = {Holmberg, Johan K and Alajbegovic, Azra and Gawlik, Kinga and Elowsson, Linda and Durbeej-Hjalt, Madeleine},
  issn         = {1663-4365},
  language     = {eng},
  number       = {Jul 3},
  publisher    = {Frontiers},
  series       = {Frontiers in Aging Neuroscience},
  title        = {Laminin α2 Chain-Deficiency is Associated with microRNA Deregulation in Skeletal Muscle and Plasma.},
  url          = {http://dx.doi.org/10.3389/fnagi.2014.00155},
  volume       = {6},
  year         = {2014},
}