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miR-146a deficiency does not aggravate muscular dystrophy in mdx mice

Duchenne muscular dystrophy (DMD) is a genetic disease evoked by a mutation in the dystrophin gene. It is associated with progressive muscle degeneration and increased inflammation. Up to this date, mainly anti-inflammatory treatment is available for patients suffering from DMD. miR-146a is known to...

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Autores principales: Bronisz-Budzyńska, Iwona, Chwalenia, Katarzyna, Mucha, Olga, Podkalicka, Paulina, Karolina-Bukowska-Strakova, Józkowicz, Alicja, Łoboda, Agnieszka, Kozakowska, Magdalena, Dulak, Józef
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693262/
https://www.ncbi.nlm.nih.gov/pubmed/31412923
http://dx.doi.org/10.1186/s13395-019-0207-0
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author Bronisz-Budzyńska, Iwona
Chwalenia, Katarzyna
Mucha, Olga
Podkalicka, Paulina
Karolina-Bukowska-Strakova
Józkowicz, Alicja
Łoboda, Agnieszka
Kozakowska, Magdalena
Dulak, Józef
author_facet Bronisz-Budzyńska, Iwona
Chwalenia, Katarzyna
Mucha, Olga
Podkalicka, Paulina
Karolina-Bukowska-Strakova
Józkowicz, Alicja
Łoboda, Agnieszka
Kozakowska, Magdalena
Dulak, Józef
author_sort Bronisz-Budzyńska, Iwona
collection PubMed
description Duchenne muscular dystrophy (DMD) is a genetic disease evoked by a mutation in the dystrophin gene. It is associated with progressive muscle degeneration and increased inflammation. Up to this date, mainly anti-inflammatory treatment is available for patients suffering from DMD. miR-146a is known to diminish inflammation and fibrosis in different tissues by downregulating the expression of proinflammatory cytokines. However, its role in DMD has not been studied so far. In our work, we have generated mice globally lacking both dystrophin and miR-146a (miR-146a(−/−)mdx) and examined them together with wild-type, single miR-146a knockout and dystrophic (mdx—lacking dystrophin) mice in a variety of aspects associated with DMD pathophysiology (muscle degeneration, inflammatory reaction, muscle satellite cells, muscle regeneration, and fibrosis). We have shown that miR-146a level is increased in dystrophic muscles in comparison to wild-type mice. Its deficiency augments the expression of proinflammatory cytokines (IL-1β, CCL2, TNFα). However, muscle degeneration was not significantly worsened in mdx mice lacking miR-146a up to 24 weeks of age, although some aggravation of muscle damage and inflammation was evident in 12-week-old animals, though no effect of miR-146a deficiency was visible on quantity, proliferation, and in vitro differentiation of muscle satellite cells isolated from miR-146a(−/−)mdx mice vs. mdx. Similarly, muscle regeneration and collagen deposition were not changed by miR-146a deficiency. Nevertheless, the lack of miR-146a is associated with decreased Vegfa and increased Tgfb1. Overall, the lack of miR-146a did not aggravate significantly the dystrophic conditions in mdx mice, but its effect on DMD in more severe conditions warrants further investigation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13395-019-0207-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-66932622019-08-19 miR-146a deficiency does not aggravate muscular dystrophy in mdx mice Bronisz-Budzyńska, Iwona Chwalenia, Katarzyna Mucha, Olga Podkalicka, Paulina Karolina-Bukowska-Strakova Józkowicz, Alicja Łoboda, Agnieszka Kozakowska, Magdalena Dulak, Józef Skelet Muscle Research Duchenne muscular dystrophy (DMD) is a genetic disease evoked by a mutation in the dystrophin gene. It is associated with progressive muscle degeneration and increased inflammation. Up to this date, mainly anti-inflammatory treatment is available for patients suffering from DMD. miR-146a is known to diminish inflammation and fibrosis in different tissues by downregulating the expression of proinflammatory cytokines. However, its role in DMD has not been studied so far. In our work, we have generated mice globally lacking both dystrophin and miR-146a (miR-146a(−/−)mdx) and examined them together with wild-type, single miR-146a knockout and dystrophic (mdx—lacking dystrophin) mice in a variety of aspects associated with DMD pathophysiology (muscle degeneration, inflammatory reaction, muscle satellite cells, muscle regeneration, and fibrosis). We have shown that miR-146a level is increased in dystrophic muscles in comparison to wild-type mice. Its deficiency augments the expression of proinflammatory cytokines (IL-1β, CCL2, TNFα). However, muscle degeneration was not significantly worsened in mdx mice lacking miR-146a up to 24 weeks of age, although some aggravation of muscle damage and inflammation was evident in 12-week-old animals, though no effect of miR-146a deficiency was visible on quantity, proliferation, and in vitro differentiation of muscle satellite cells isolated from miR-146a(−/−)mdx mice vs. mdx. Similarly, muscle regeneration and collagen deposition were not changed by miR-146a deficiency. Nevertheless, the lack of miR-146a is associated with decreased Vegfa and increased Tgfb1. Overall, the lack of miR-146a did not aggravate significantly the dystrophic conditions in mdx mice, but its effect on DMD in more severe conditions warrants further investigation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13395-019-0207-0) contains supplementary material, which is available to authorized users. BioMed Central 2019-08-14 /pmc/articles/PMC6693262/ /pubmed/31412923 http://dx.doi.org/10.1186/s13395-019-0207-0 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Bronisz-Budzyńska, Iwona
Chwalenia, Katarzyna
Mucha, Olga
Podkalicka, Paulina
Karolina-Bukowska-Strakova
Józkowicz, Alicja
Łoboda, Agnieszka
Kozakowska, Magdalena
Dulak, Józef
miR-146a deficiency does not aggravate muscular dystrophy in mdx mice
title miR-146a deficiency does not aggravate muscular dystrophy in mdx mice
title_full miR-146a deficiency does not aggravate muscular dystrophy in mdx mice
title_fullStr miR-146a deficiency does not aggravate muscular dystrophy in mdx mice
title_full_unstemmed miR-146a deficiency does not aggravate muscular dystrophy in mdx mice
title_short miR-146a deficiency does not aggravate muscular dystrophy in mdx mice
title_sort mir-146a deficiency does not aggravate muscular dystrophy in mdx mice
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693262/
https://www.ncbi.nlm.nih.gov/pubmed/31412923
http://dx.doi.org/10.1186/s13395-019-0207-0
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