%0 Journal Article
%T Laminin ¦Á2 chain-deficiency is associated with microRNA deregulation in skeletal muscle and plasma
%A Johan Holmberg
%A Azra Alajbegovic
%A Kinga I. Gawlik
%A Madeleine Durbeej
%J Frontiers in Aging Neuroscience
%D 2014
%I Frontiers Media
%R 10.3389/fnagi.2014.00155
%X 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 ¦Á2 chain. To gain insight into the pathophysiological roles of miRNAs associated with MDC1A pathology, laminin ¦Á2 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 ¦Á2 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 ¦Á2 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.
%K Fibrosis
%K Inflammation
%K Laminin
%K MDC1A
%K microRNA
%K Muscular Dystrophy
%K Animal
%U http://www.frontiersin.org/Journal/10.3389/fnagi.2014.00155/abstract