Absence of microRNA-21 does not reduce muscular dystrophy in mouse models of LAMA2-CMD

作者：Oliveira Bernardo Moreira Soares^*; Durbeej Madeleine; Holmberg Johan

来源：PLos One, 2017, 12(8): e0181950.

DOI：10.1371/journal.pone.0181950

MicroRNAs (miRNAs) are short non-coding RNAs that modulate gene expression post-transcriptionally. Current evidence suggests that miR-21 plays a significant role in the progression of fibrosis in muscle diseases. Laminin-deficient congenital muscular dystrophy (LAMA2-CMD) is a severe form of congenital muscular dystrophy caused by mutations in the gene encoding laminin alpha 2 chain. Mouse models dy(3K)/dy(3K) and dy(2J)/dy(2J), respectively, adequately mirror severe and milder forms of LAMA2-CMD. Both human and mouse LAMA2-CMD muscles are characterized by extensive fibrosis and considering that fibrosis is the final step that destroys muscle during the disease course, anti-fibrotic therapies may be effective strategies for prevention of LAMA2-CMD. We have previously demonstrated a significant up-regulation of the pro-fibrotic miR-21 in dy(3K)/dy(3K) and dy(2J)/dy(2J) skeletal muscle. Hence, the objective of this study was to explore if absence of miR-21 reduces fibrogenesis and improves the phenotype of LAMA2-CMD mice. Thus, we generated dy(3K)/dy(3K) and dy(2J)/dy(2J) mice devoid of miR-21 (dy(3K)/miR-21 and dy(2J)/miR-21 mice, respectively). However, the muscular dystrophy phenotype of dy(3K)/miR-21 and dy(2J)/miR-21 double knock-out mice was not improved compared to dy(3K)/dy(3K) or dy(2J)/dy(2J) mice, respectively. Mice displayed the same body weight, dystrophic muscles (with fibrosis) and impaired muscle function. These data indicate that miR-21 may not be involved in the development of fibrosis in LAMA2-CMD.

• 出版日期2017-8-3