The microRNA, miR-133b, functions to slow Duchenne muscular dystrophy pathogenesis

AbstractDuchenne muscular dystrophy (DMD) is characterized by progressive degeneration of skeletal muscles. To date, there are no treatments available to slow or prevent the disease. Hence, it remains essential to identify molecular factors that promote muscle biogenesis since they could serve as therapeutic targets for treating DMD. While the muscle enriched microRNA, miR-133b, has been implicated in the biogenesis of muscle fibers, its role in DMD remains unknown. To assess the role of miR-133b in DMD-affected skeletal muscles, we genetically ablated miR-133b in the mdx mouse model of DMD. In the absence of miR-133b, the tibialis anterior muscle of juvenile and adult mdx mice is populated by small muscle fibers with centralized nuclei, exhibits increased fibrosis, and thickened interstitial space. Additional analysis revealed that loss of miR-133b exacerbates DMD-pathogenesis partly by altering the number of satellite cells and levels of protein-encoding genes, including previously identified miR-133b targets as well as genes involved in cell proliferation and fibrosis. Altogether, our data demonstrate that skeletal muscles utilize miR-133b to mitigate the deleterious effects of DMD.

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Have Duchenne Muscular Dystrophy Patients an Increased Cancer Risk?

Journal of Neuromuscular Diseases ◽

10.3233/jnd-210676 ◽

2021 ◽

pp. 1-5

Author(s):

Gian Luca Vita ◽

Luisa Politano ◽

Angela Berardinelli ◽

Giuseppe Vita

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Systematic Investigation ◽

Mdx Mice ◽

True Incidence ◽

Patients With Cancer ◽

Dmd Gene ◽

Age Range ◽

Prevalence Of Cancer

Background: Increasing evidence suggests that Duchenne muscular dystrophy (DMD) gene is involved in the occurrence of different types of cancer. Moreover, development of sarcomas was reported in mdx mice, the murine model of DMD, in older age. So far, nine isolated DMD patients were reported with concomitant cancer, four of whom with rhabdomyosarcoma (RMS), but no systematic investigation was performed about the true incidence of cancer in DMD. Methods: All members of the Italian Association of Myology were asked about the occurrence of cancer in their DMD patients in the last 30 years. Results: Four DMD patients with cancer were reported after checking 2455 medical records. One developed brain tumour at the age of 35 years. Two patients had alveolar RMS at 14 and 17 years of age. The fourth patient had a benign enchondroma when 11-year-old. Conclusion: Prevalence of cancer in general in the Italian DMD patients does not seem to be different from that in the general population with the same age range. Although the small numbers herein presented do not allow definitive conclusion, the frequent occurrence of RMS in DMD patients raises an alert for basic researchers and clinicians. The role of DMD gene in cancer merits further investigations.

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In vivo genome editing in mouse restores dystrophin expression in Duchenne muscular dystrophy patient muscle fibers

Genome Medicine ◽

10.1186/s13073-021-00876-0 ◽

2021 ◽

Vol 13 (1) ◽

Cited By ~ 1

Author(s):

Menglong Chen ◽

Hui Shi ◽

Shixue Gou ◽

Xiaomin Wang ◽

Lei Li ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Mouse Model ◽

Genome Editing ◽

Large Scale ◽

Gene Editing ◽

High Efficiency ◽

Muscle Fibers ◽

Muscle Cells

Abstract Background Mutations in the DMD gene encoding dystrophin—a critical structural element in muscle cells—cause Duchenne muscular dystrophy (DMD), which is the most common fatal genetic disease. Clustered regularly interspaced short palindromic repeat (CRISPR)-mediated gene editing is a promising strategy for permanently curing DMD. Methods In this study, we developed a novel strategy for reframing DMD mutations via CRISPR-mediated large-scale excision of exons 46–54. We compared this approach with other DMD rescue strategies by using DMD patient-derived primary muscle-derived stem cells (DMD-MDSCs). Furthermore, a patient-derived xenograft (PDX) DMD mouse model was established by transplanting DMD-MDSCs into immunodeficient mice. CRISPR gene editing components were intramuscularly delivered into the mouse model by adeno-associated virus vectors. Results Results demonstrated that the large-scale excision of mutant DMD exons showed high efficiency in restoring dystrophin protein expression. We also confirmed that CRISPR from Prevotella and Francisella 1(Cas12a)-mediated genome editing could correct DMD mutation with the same efficiency as CRISPR-associated protein 9 (Cas9). In addition, more than 10% human DMD muscle fibers expressed dystrophin in the PDX DMD mouse model after treated by the large-scale excision strategies. The restored dystrophin in vivo was functional as demonstrated by the expression of the dystrophin glycoprotein complex member β-dystroglycan. Conclusions We demonstrated that the clinically relevant CRISPR/Cas9 could restore dystrophin in human muscle cells in vivo in the PDX DMD mouse model. This study demonstrated an approach for the application of gene therapy to other genetic diseases.

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ROLE OF PANCHAKARMA IN DUCHENNE MUSCULAR DYSTROPHY

International Journal of Research in Ayurveda and Pharmacy ◽

10.7897/2277-4343.04238 ◽

2013 ◽

Vol 4 (2) ◽

pp. 272-275

Author(s):

Ashutosh Chaturvedi ◽

Prasanna N Rao ◽

Shailaja U ◽

M Ashvini Kumar

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy

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Effect of Duchenne muscular dystrophy on enzymes of energy metabolism in individual muscle fibers

Metabolism ◽

10.1016/0026-0495(87)90113-2 ◽

1987 ◽

Vol 36 (8) ◽

pp. 761-767 ◽

Cited By ~ 34

Author(s):

Maggie M.-Y. Chi ◽

Carol S. Hintz ◽

Deidre McKee ◽

Steven Felder ◽

Natasha Grant ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Energy Metabolism ◽

Muscular Dystrophy ◽

Muscle Fibers ◽

Individual Muscle ◽

Enzymes Of Energy Metabolism

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Induced Pluripotent Stem Cells for Duchenne Muscular Dystrophy Modeling and Therapy

Cells ◽

10.3390/cells7120253 ◽

2018 ◽

Vol 7 (12) ◽

pp. 253 ◽

Cited By ~ 15

Author(s):

Lubos Danisovic ◽

Martina Culenova ◽

Maria Csobonyeiova

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Pluripotent Stem Cells ◽

Pluripotent Stem Cell ◽

Induced Pluripotent Stem Cell ◽

Cell Reprogramming ◽

Progressive Degeneration ◽

Cardiac Muscles ◽

Dmd Gene ◽

Induced Pluripotent

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder, caused by mutation of the DMD gene which encodes the protein dystrophin. This dystrophin defect leads to the progressive degeneration of skeletal and cardiac muscles. Currently, there is no effective therapy for this disorder. However, the technology of cell reprogramming, with subsequent controlled differentiation to skeletal muscle cells or cardiomyocytes, may provide a unique tool for the study, modeling, and treatment of Duchenne muscular dystrophy. In the present review, we describe current methods of induced pluripotent stem cell generation and discuss their implications for the study, modeling, and development of cell-based therapies for Duchenne muscular dystrophy.

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Mast cells in the pathophysiology of Duchenne muscular dystrophy in Golden Retriever dogs

Pesquisa Veterinária Brasileira ◽

10.1590/1678-5150-pvb-6340 ◽

2020 ◽

Vol 40 (10) ◽

pp. 791-797

Author(s):

Isabela M. Martins ◽

Lygia M.M. Malvestio ◽

Jair R. Engracia-Filho ◽

Gustavo S. Claudiano ◽

Flávio R. Moraes ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Mast Cells ◽

Muscular Dystrophy ◽

Fibrous Tissue ◽

Control Group ◽

Golden Retriever ◽

Collagenous Tissue ◽

Muscle Types ◽

Muscle Groups

ABSTRACT: The Golden Retriever muscular dystrophy (GRMD) is one of the best models of Duchenne muscular dystrophy (DMD), with similar genotypic and phenotypic manifestations. Progressive proliferation of connective tissue in the endomysium of the muscle fibers occurs in parallel with the clinical course of the disease in GRMD animals. Previous studies suggest a relationship between mast cells and the deposition of fibrous tissue due to the release of mediators that recruit fibroblasts. The aim of this study was to evaluate the presence of mast cells and their relationship with muscle injury and fibrosis in GRMD dogs of different ages. Samples of muscle groups from six GRMD and four control dogs, aged 2 to 8 months, were collected and analyzed. The samples were processed and stained with HE, toluidine blue, and Azan trichrome. Our results showed that there was a significant increase in infiltration of mast cells in all muscle groups of GRMD dogs compared to the control group. The average number of mast cells, as well as the deposition of fibrous tissue, decreased with age in GRMD dogs. In the control group, all muscle types showed a significant increase in the amount of collagenous tissue. This suggests increased mast cell degranulation occurred in younger GRMD dogs, resulting in increased interstitial space and fibrous tissue in muscle, which then gradually decreased over time as the dogs aged. However, further studies are needed to clarify the role of mast cells in the pathogenesis of fibrosis.

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Light and ripening-regulated BBX protein-encoding genes in Solanum lycopersicum

Scientific Reports ◽

10.1038/s41598-020-76131-0 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Bruno Silvestre Lira ◽

Maria José Oliveira ◽

Lumi Shiose ◽

Raquel Tsu Ay Wu ◽

Daniele Rosado ◽

...

Keyword(s):

Tomato Fruit ◽

Protein Family ◽

Tomato Genome ◽

Physiological Processes ◽

Fruit Development And Ripening ◽

Protein Encoding ◽

Ripening Inhibitor ◽

Encoding Genes ◽

Signalling Cascade

Abstract Light controls several aspects of plant development through a complex signalling cascade. Several B-box domain containing proteins (BBX) were identified as regulators of Arabidopsis thaliana seedling photomorphogenesis. However, the knowledge about the role of this protein family in other physiological processes and species remains scarce. To fill this gap, here BBX protein encoding genes in tomato genome were characterised. The robust phylogeny obtained revealed how the domain diversity in this protein family evolved in Viridiplantae and allowed the precise identification of 31 tomato SlBBX proteins. The mRNA profiling in different organs revealed that SlBBX genes are regulated by light and their transcripts accumulation is directly affected by the chloroplast maturation status in both vegetative and fruit tissues. As tomato fruits develops, three SlBBXs were found to be upregulated in the early stages, controlled by the proper chloroplast differentiation and by the PHYTOCHROME (PHY)-dependent light perception. Upon ripening, other three SlBBXs were transcriptionally induced by RIPENING INHIBITOR master transcriptional factor, as well as by PHY-mediated signalling and proper plastid biogenesis. Altogether, the results obtained revealed a conserved role of SlBBX gene family in the light signalling cascade and identified putative members affecting tomato fruit development and ripening.

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