miR-146a deficiency does not aggravate muscular dystrophy in mdx mice
Abstract 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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-08-01
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| Series: | Skeletal Muscle |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13395-019-0207-0 |
| _version_ | 1818510936364810240 |
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| author | Iwona Bronisz-Budzyńska Katarzyna Chwalenia Olga Mucha Paulina Podkalicka Karolina-Bukowska-Strakova Alicja Józkowicz Agnieszka Łoboda Magdalena Kozakowska Józef Dulak |
| author_facet | Iwona Bronisz-Budzyńska Katarzyna Chwalenia Olga Mucha Paulina Podkalicka Karolina-Bukowska-Strakova Alicja Józkowicz Agnieszka Łoboda Magdalena Kozakowska Józef Dulak |
| author_sort | Iwona Bronisz-Budzyńska |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-10T23:26:47Z |
| format | Article |
| id | doaj.art-175c5c5bbe5442d28ac094fd7588e154 |
| institution | Directory Open Access Journal |
| issn | 2044-5040 |
| language | English |
| last_indexed | 2024-12-10T23:26:47Z |
| publishDate | 2019-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Skeletal Muscle |
| spelling | doaj.art-175c5c5bbe5442d28ac094fd7588e1542022-12-22T01:29:33ZengBMCSkeletal Muscle2044-50402019-08-019111710.1186/s13395-019-0207-0miR-146a deficiency does not aggravate muscular dystrophy in mdx miceIwona Bronisz-Budzyńska0Katarzyna Chwalenia1Olga Mucha2Paulina Podkalicka3Karolina-Bukowska-Strakova4Alicja Józkowicz5Agnieszka Łoboda6Magdalena Kozakowska7Józef Dulak8Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian UniversityDepartment of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian UniversityDepartment of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian UniversityDepartment of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian UniversityDepartment of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian UniversityDepartment of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian UniversityDepartment of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian UniversityDepartment of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian UniversityDepartment of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian UniversityAbstract 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.http://link.springer.com/article/10.1186/s13395-019-0207-0miR-146aSkeletal musclemdxDuchenne muscular dystrophyInflammationRegeneration |
| spellingShingle | Iwona Bronisz-Budzyńska Katarzyna Chwalenia Olga Mucha Paulina Podkalicka Karolina-Bukowska-Strakova Alicja Józkowicz Agnieszka Łoboda Magdalena Kozakowska Józef Dulak miR-146a deficiency does not aggravate muscular dystrophy in mdx mice Skeletal Muscle miR-146a Skeletal muscle mdx Duchenne muscular dystrophy Inflammation Regeneration |
| 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 | miR-146a Skeletal muscle mdx Duchenne muscular dystrophy Inflammation Regeneration |
| url | http://link.springer.com/article/10.1186/s13395-019-0207-0 |
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