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

Moreira Soares Oliveira, Bernardo LU ; Durbeej, Madeleine LU and Holmberg, Johan LU (2017) In PLoS ONE 12(8).
Abstract

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 α2 chain. Mouse models dy3K/dy3K and dy2J/dy2J, 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... (More)

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 α2 chain. Mouse models dy3K/dy3K and dy2J/dy2J, 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 dy3K/dy3K and dy2J/dy2J 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 dy3K/dy3K and dy2J/dy2J mice devoid of miR-21 (dy3K/miR-21 and dy2J/miR-21 mice, respectively). However, the muscular dystrophy phenotype of dy3K/miR-21 and dy2J/miR-21 double knock-out mice was not improved compared to dy3K/dy3K or dy2J/dy2J 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.

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published
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in
PLoS ONE
volume
12
issue
8
publisher
Public Library of Science
external identifiers
  • scopus:85026783477
  • wos:000406853600047
ISSN
1932-6203
DOI
10.1371/journal.pone.0181950
language
English
LU publication?
yes
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7d9158db-0600-49d2-a345-f04b52130aba
date added to LUP
2017-08-22 11:01:48
date last changed
2018-06-10 05:22:15
@article{7d9158db-0600-49d2-a345-f04b52130aba,
  abstract     = {<p>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 α2 chain. Mouse models dy<sup>3K</sup>/dy<sup>3K</sup> and dy<sup>2J</sup>/dy<sup>2J</sup>, 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<sup>3K</sup>/dy<sup>3K</sup> and dy<sup>2J</sup>/dy<sup>2J</sup> 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<sup>3K</sup>/dy<sup>3K</sup> and dy<sup>2J</sup>/dy<sup>2J</sup> mice devoid of miR-21 (dy<sup>3K</sup>/miR-21 and dy<sup>2J</sup>/miR-21 mice, respectively). However, the muscular dystrophy phenotype of dy<sup>3K</sup>/miR-21 and dy<sup>2J</sup>/miR-21 double knock-out mice was not improved compared to dy<sup>3K</sup>/dy<sup>3K</sup> or dy<sup>2J</sup>/dy<sup>2J</sup> 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.</p>},
  articleno    = {e0181950},
  author       = {Moreira Soares Oliveira, Bernardo and Durbeej, Madeleine and Holmberg, Johan},
  issn         = {1932-6203},
  language     = {eng},
  month        = {08},
  number       = {8},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Absence of microRNA-21 does not reduce muscular dystrophy in mouse models of LAMA2-CMD},
  url          = {http://dx.doi.org/10.1371/journal.pone.0181950},
  volume       = {12},
  year         = {2017},
}