Lack of miR-378 attenuates muscular dystrophy in mdx mice
| العنوان: | Lack of miR-378 attenuates muscular dystrophy in mdx mice |
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| المؤلفون: | Magdalena Kozakowska, Paulina Podkalicka, Katarzyna Pietraszek-Gremplewicz, Jozef Dulak, Urszula Głowniak-Kwitek, Michal Mikula, Anna Kostera-Pruszczyk, Olga Mucha, Jerzy Ostrowski, Agnieszka Łoboda, Maciej Cieśla, Alicja Jozkowicz, Karolina Bukowska-Strakova, Maria Kulecka, Iwona Bronisz-Budzyńska, Anna Potulska-Chromik, Anna Cetnarowska |
| المصدر: | JCI Insight |
| بيانات النشر: | American Society for Clinical Investigation, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | musculoskeletal diseases, 0301 basic medicine, medicine.medical_specialty, Satellite Cells, Skeletal Muscle, Noncoding RNAs, Duchenne muscular dystrophy, Down-Regulation, Inflammation, Transcriptome, Mice, 03 medical and health sciences, Gastrocnemius muscle, 0302 clinical medicine, Fibrosis, Internal medicine, medicine, Animals, Muscular dystrophy, Muscle, Skeletal, Mice, Knockout, biology, business.industry, General Medicine, FGF1, medicine.disease, Muscular Dystrophy, Duchenne, MicroRNAs, 030104 developmental biology, Endocrinology, 030220 oncology & carcinogenesis, Muscle Biology, Mice, Inbred mdx, biology.protein, Muscle, Fibroblast Growth Factor 1, medicine.symptom, business, Dystrophin, Research Article, Genetic diseases |
| الوصف: | The severity of Duchenne muscular dystrophy (DMD), an incurable disease caused by the lack of dystrophin, might be modulated by different factors, including miRNAs. Among them, miR-378 is considered of high importance for muscle biology, but intriguingly, its role in DMD and its murine model (mdx mice) has not been thoroughly addressed so far. Here, we demonstrate that dystrophic mice additionally globally lacking miR-378 (double-KO [dKO] animals) exhibited better physical performance and improved absolute muscle force compared with mdx mice. Accordingly, markers of muscle damage in serum were significantly decreased in dKO mice, accompanied by diminished inflammation, fibrosis, and reduced abundance of regenerating fibers within muscles. The lack of miR-378 also normalized the aggravated fusion of dystrophin-deficient muscle satellite cells (mSCs). RNA sequencing of gastrocnemius muscle transcriptome revealed fibroblast growth factor 1 (Fgf1) as one of the most significantly downregulated genes in mice devoid of miR-378, indicating FGF1 as one of the mediators of changes driven by the lack of miR-378. In conclusion, we suggest that targeting miR-378 has the potential to ameliorate DMD pathology. miR-378 deficiency improves the dystrophic phenotype in mdx mice, suggesting that modulation of miR-378 level may be a potential approach to attenuate DMD severity. |
| تدمد: | 2379-3708 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::393619b978ccae3831660254c3df6793Test https://doi.org/10.1172/jci.insight.135576Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....393619b978ccae3831660254c3df6793 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23793708 |
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