Absence of microRNA-21 does not reduce muscular dystrophy in mouse models of LAMA2-CMD
(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.
(Less)
- author
- Moreira Soares Oliveira, Bernardo LU ; Durbeej, Madeleine LU and Holmberg, Johan LU
- organization
- publishing date
- 2017-08-01
- 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
- 2024-09-02 05:33:35
@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}}, }