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

Moreira Soares Oliveira, Bernardo LU orcid ; 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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publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
12
issue
8
article number
e0181950
publisher
Public Library of Science (PLoS)
external identifiers
  • pmid:28771630
  • wos:000406853600047
  • scopus:85026783477
ISSN
1932-6203
DOI
10.1371/journal.pone.0181950
language
English
LU publication?
yes
id
7d9158db-0600-49d2-a345-f04b52130aba
date added to LUP
2017-08-22 11:01:48
date last changed
2024-04-14 16:08:19
@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>}},
  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 (PLoS)}},
  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}},
  doi          = {{10.1371/journal.pone.0181950}},
  volume       = {{12}},
  year         = {{2017}},
}