Splicing in two skeletal muscle transcripts correlates with clinical phenotype in myotonic dystrophy type 1 patients

2022 ◽  
Author(s):  
Saam Sedehizadeh ◽  
Marzena Wojciechowska ◽  
Ami Ketley ◽  
J. David Brook ◽  
Paul Maddison
Keyword(s):  
Skeletal Muscle ◽  
Myotonic Dystrophy ◽  
Clinical Phenotype ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type

scholarly journals Training program-induced skeletal muscle adaptations in two men with myotonic dystrophy type 1

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Marie-Pier Roussel ◽  
Marika Morin ◽  
Mélina Girardin ◽  
Anne-Marie Fortin ◽  
Mario Leone ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Training Program ◽  
Myotonic Dystrophy ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Muscle Adaptations ◽  
Skeletal Muscle Adaptations

scholarly journals Most expression and splicing changes in myotonic dystrophy type 1 and type 2 skeletal muscle are shared with other muscular dystrophies

2014 ◽  
Vol 24 (3) ◽  
pp. 227-240 ◽  
Author(s):  
Linda L. Bachinski ◽  
Keith A. Baggerly ◽  
Valerie L. Neubauer ◽  
Tamara J. Nixon ◽  
Olayinka Raheem ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Myotonic Dystrophy ◽  
Muscular Dystrophies ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type

Risk Prediction for Clinical Phenotype in Myotonic Dystrophy Type 1: Data from 2,650 Patients

2007 ◽  
Vol 11 (1) ◽  
pp. 84-90 ◽  
Author(s):  
Leila Baghernajad Salehi ◽  
Emanuela Bonifazi ◽  
Enrico Di Stasio ◽  
Massimo Gennarelli ◽  
Annalisa Botta ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Risk Prediction ◽  
Clinical Phenotype ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type

scholarly journals Inhibition of Postn Rescues Myogenesis Defects in Myotonic Dystrophy Type 1 Myoblast Model

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaopeng Shen ◽  
Zhongxian Liu ◽  
Chunguang Wang ◽  
Feng Xu ◽  
Jingyi Zhang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Myotonic Dystrophy ◽  
Cell Model ◽  
Neutralizing Antibody ◽  
Underlying Mechanism ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Ctg Repeats ◽  
Myoblast Cells

Myotonic dystrophy type 1 (DM1) is an inherited neuromuscular disease caused by expanded CTG repeats in the 3′ untranslated region (3′UTR) of the DMPK gene. The myogenesis process is defective in DM1, which is closely associated with progressive muscle weakness and wasting. Despite many proposed explanations for the myogenesis defects in DM1, the underlying mechanism and the involvement of the extracellular microenvironment remained unknown. Here, we constructed a DM1 myoblast cell model and reproduced the myogenesis defects. By RNA sequencing (RNA-seq), we discovered that periostin (Postn) was the most significantly upregulated gene in DM1 myogenesis compared with normal controls. This difference in Postn was confirmed by real-time quantitative PCR (RT-qPCR) and western blotting. Moreover, Postn was found to be significantly upregulated in skeletal muscle and myoblasts of DM1 patients. Next, we knocked down Postn using a short hairpin RNA (shRNA) in DM1 myoblast cells and found that the myogenesis defects in the DM1 group were successfully rescued, as evidenced by increases in the myotube area, the fusion index, and the expression of myogenesis regulatory genes. Similarly, Postn knockdown in normal myoblast cells enhanced myogenesis. As POSTN is a secreted protein, we treated the DM1 myoblast cells with a POSTN-neutralizing antibody and found that DM1 myogenesis defects were successfully rescued by POSTN neutralization. We also tested the myogenic ability of myoblasts in the skeletal muscle injury mouse model and found that Postn knockdown improved the myogenic ability of DM1 myoblasts. The activity of the TGF-β/Smad3 pathway was upregulated during DM1 myogenesis but repressed when inhibiting Postn with a Postn shRNA or a POSTN-neutralizing antibody, which suggested that the TGF-β/Smad3 pathway might mediate the function of Postn in DM1 myogenesis. These results suggest that Postn is a potential therapeutical target for the treatment of myogenesis defects in DM1.

scholarly journals Overexpression of CUGBP1 in Skeletal Muscle from Adult Classic Myotonic Dystrophy Type 1 but Not from Myotonic Dystrophy Type 2

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e83777 ◽  
Author(s):  
Rosanna Cardani ◽  
Enrico Bugiardini ◽  
Laura V. Renna ◽  
Giulia Rossi ◽  
Graziano Colombo ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Myotonic Dystrophy ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Myotonic Dystrophy Type 2

scholarly journals MBNL1 reverses the proliferation defect of skeletal muscle satellite cells in myotonic dystrophy type 1 by inhibiting autophagy via the mTOR pathway

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Kai-Yi Song ◽  
Xiu-Ming Guo ◽  
Hui-Qi Wang ◽  
Lei Zhang ◽  
Si-Yuan Huang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Myotonic Dystrophy ◽  
Muscle Atrophy ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Skeletal Muscle Regeneration ◽  
Skeletal Muscle Atrophy ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type

Abstract Skeletal muscle atrophy is one of the clinical symptoms of myotonic dystrophy type 1 (DM1). A decline in skeletal muscle regeneration is an important contributor to muscle atrophy. Skeletal muscle satellite cells (SSCs) drive skeletal muscle regeneration. Increased autophagy can reduce the proliferative capacity of SSCs, which plays an important role in the early regeneration of damaged skeletal muscle in DM1. Discovering new ways to restore SSC proliferation may aid in the identification of new therapeutic targets for the treatment of skeletal muscle atrophy in DM1. In the pathogenesis of DM1, muscleblind-like 1 (MBNL1) protein is generally considered to form nuclear RNA foci and disturb the RNA-splicing function. However, the role of MBNL1 in SSC proliferation in DM1 has not been reported. In this study, we obtained SSCs differentiated from normal DM1-04-induced pluripotent stem cells (iPSCs), DM1-03 iPSCs, and DM1-13-3 iPSCs edited by transcription activator-like (TAL) effector nucleases (TALENs) targeting CTG repeats, and primary SSCs to study the pathogenesis of DM1. DM1 SSC lines and primary SSCs showed decreased MBNL1 expression and elevated autophagy levels. However, DM1 SSCs edited by TALENs showed increased cytoplasmic distribution of MBNL1, reduced levels of autophagy, increased levels of phosphorylated mammalian target of rapamycin (mTOR), and improved proliferation rates. In addition, we confirmed that after MBNL1 overexpression, the proliferative capability of DM1 SSCs and the level of phosphorylated mTOR were enhanced, while the autophagy levels were decreased. Our data also demonstrated that the proliferative capability of DM1 SSCs was enhanced after autophagy was inhibited by overexpressing mTOR. Finally, treatment with rapamycin (an mTOR inhibitor) was shown to abolish the increased proliferation capability of DM1 SSCs due to MBNL1 overexpression. Taken together, these data suggest that MBNL1 reverses the proliferation defect of SSCs in DM1 by inhibiting autophagy via the mTOR pathway.

scholarly journals Intrinsic Myogenic Potential of Skeletal Muscle-Derived Pericytes from Patients with Myotonic Dystrophy Type 1

2019 ◽  
Vol 15 ◽  
pp. 120-132 ◽  
Author(s):  
Cornelia Rosanne Maria Ausems ◽  
Renée Henrica Lamberta Raaijmakers ◽  
Walterus Johannes Antonius Adriana van den Broek ◽  
Marieke Willemse ◽  
Baziel Gerardus Maria van Engelen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Myotonic Dystrophy ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Myogenic Potential
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