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Novel Molecular Approaches to Skeletal Muscle Disease and Disuse 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (18 August 2023) | Viewed by 11982

Special Issue Editor


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Guest Editor
1. Max-Planck-Institute of Biochemistry, 82152 Martinsried, Germany
2. Department of Biomedical Science, University of Padova, 35121 Padua, Italy
Interests: mass spectrometry-based proteomics; skeletal muscle; muscle disease; space medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

I am delighted to announce a call for submissions to a Special Issue of the International Journal of Molecular Sciences, entitled “Novel Molecular Approaches to Skeletal Muscle Disease and Disuse 2.0”. Muscle-specific diseases with a variety of genetic and acquired causes, as well as aging and metabolic disorders, impair the function of skeletal muscle. This has consequences that extend far beyond muscle itself, with a systemic impact on the quality of life. Exercise can be an important non-pharmacological therapeutic intervention counteracting the effects of disuse; however, mechanistic knowledge on muscle physiopathology can improve its applicability and ensure greater success. With this Special Issue, we aim to illuminate the impacts of omics technologies on the system analysis of muscle disease. We are looking for transcriptomics, proteomics, and metabolomic studies which tackle different aspects of muscle disuse and therapeutic interventions. In addition, we intend to show how new molecular approaches, technologies, and disease models are channeling invaluable information that supports translational research and novel therapeutic approaches.

Following the success of Volume 1 of Special Issue “Novel Molecular Approaches to Skeletal Muscle Disease and Disuse”, we reopen this issue again in the International Journal of Molecular Sciences (https://www.mdpi.com/journal/ijms, ISSN 1422-0067, IF 5.924, JCR Category Q1). This second Special Issue will host original research articles, as well as reviews and meta-analyses, of omics data on all aspects of muscle disease and disuse.

https://www.mdpi.com/journal/ijms/special_issues/Approaches_Skeletal_Muscle

Dr. Marta Murgia
Guest Editor

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Keywords

  • skeletal muscle
  • proteomics
  • metabolomics
  • transcriptomics
  • exercise intervention
  • systems biology
  • disease models

Published Papers (4 papers)

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Research

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25 pages, 3878 KiB  
Article
Space Omics and Tissue Response in Astronaut Skeletal Muscle after Short and Long Duration Missions
by Dieter Blottner, Manuela Moriggi, Gabor Trautmann, Maria Hastermann, Daniele Capitanio, Enrica Torretta, Katharina Block, Joern Rittweger, Ulrich Limper, Cecilia Gelfi and Michele Salanova
Int. J. Mol. Sci. 2023, 24(4), 4095; https://doi.org/10.3390/ijms24044095 - 17 Feb 2023
Cited by 8 | Viewed by 2657
Abstract
The molecular mechanisms of skeletal muscle adaptation to spaceflight are as yet not fully investigated and well understood. The MUSCLE BIOPSY study analyzed pre and postflight deep calf muscle biopsies (m. soleus) obtained from five male International Space Station (ISS) astronauts. Moderate rates [...] Read more.
The molecular mechanisms of skeletal muscle adaptation to spaceflight are as yet not fully investigated and well understood. The MUSCLE BIOPSY study analyzed pre and postflight deep calf muscle biopsies (m. soleus) obtained from five male International Space Station (ISS) astronauts. Moderate rates of myofiber atrophy were found in long-duration mission (LDM) astronauts (~180 days in space) performing routine inflight exercise as countermeasure (CM) compared to a short-duration mission (SDM) astronaut (11 days in space, little or no inflight CM) for reference control. Conventional H&E scout histology showed enlarged intramuscular connective tissue gaps between myofiber groups in LDM post vs. preflight. Immunoexpression signals of extracellular matrix (ECM) molecules, collagen 4 and 6, COL4 and 6, and perlecan were reduced while matrix-metalloproteinase, MMP2, biomarker remained unchanged in LDM post vs. preflight suggesting connective tissue remodeling. Large scale proteomics (space omics) identified two canonical protein pathways associated to muscle weakness (necroptosis, GP6 signaling/COL6) in SDM and four key pathways (Fatty acid β-oxidation, integrin-linked kinase ILK, Rho A GTPase RHO, dilated cardiomyopathy signaling) explicitly in LDM. The levels of structural ECM organization proteins COL6A1/A3, fibrillin 1, FBN1, and lumican, LUM, increased in postflight SDM vs. LDM. Proteins from tricarboxylic acid, TCA cycle, mitochondrial respiratory chain, and lipid metabolism mostly recovered in LDM vs. SDM. High levels of calcium signaling proteins, ryanodine receptor 1, RyR1, calsequestrin 1/2, CASQ1/2, annexin A2, ANXA2, and sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA1) pump, ATP2A, were signatures of SDM, and decreased levels of oxidative stress peroxiredoxin 1, PRDX1, thioredoxin-dependent peroxide reductase, PRDX3, or superoxide dismutase [Mn] 2, SOD2, signatures of LDM postflight. Results help to better understand the spatiotemporal molecular adaptation of skeletal muscle and provide a large scale database of skeletal muscle from human spaceflight for the better design of effective CM protocols in future human deep space exploration. Full article
(This article belongs to the Special Issue Novel Molecular Approaches to Skeletal Muscle Disease and Disuse 2.0)
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14 pages, 2284 KiB  
Article
Differential Analysis of Gly211Val and Gly286Val Mutations Affecting Sarco(endo)plasmic Reticulum Ca2+-ATPase (SERCA1) in Congenital Pseudomyotonia Romagnola Cattle
by Eylem Emek Akyürek, Francesca Busato, Leonardo Murgiano, Elisa Bianchini, Marcello Carotti, Dorianna Sandonà, Cord Drögemüller, Arcangelo Gentile and Roberta Sacchetto
Int. J. Mol. Sci. 2022, 23(20), 12364; https://doi.org/10.3390/ijms232012364 - 15 Oct 2022
Cited by 1 | Viewed by 1629
Abstract
Congenital pseudomyotonia in cattle (PMT) is a rare skeletal muscle disorder, clinically characterized by stiffness and by delayed muscle relaxation after exercise. Muscle relaxation impairment is due to defective content of the Sarco(endo)plasmic Reticulum Ca2+ ATPase isoform 1 (SERCA1) protein, caused by [...] Read more.
Congenital pseudomyotonia in cattle (PMT) is a rare skeletal muscle disorder, clinically characterized by stiffness and by delayed muscle relaxation after exercise. Muscle relaxation impairment is due to defective content of the Sarco(endo)plasmic Reticulum Ca2+ ATPase isoform 1 (SERCA1) protein, caused by missense mutations in the ATP2A1 gene. PMT represents the only mammalian model of human Brody myopathy. In the Romagnola breed, two missense variants occurring in the same allele were described, leading to Gly211Val and Gly286Val (G211V/G286V) substitutions. In this study, we analyzed the consequences of G211V and G286V mutations. Results support that the reduced amount of SERCA1 is a consequence of the G211V mutation, the G286V mutation almost being benign and the ubiquitin–proteasome system (UPS) being involved. After blocking the proteasome using a proteasome inhibitor, we found that the G211V mutant accumulates in cells at levels comparable to those of WT SERCA1. Our conclusion is that G211/286V mutations presumably originate in a folding-defective SERCA1 protein, recognized and diverted to degradation by UPS, although still catalytically functional, and that the main role is played by G211V mutation. Rescue of mutated SERCA1 to the sarcoplasmic reticulum membrane can re-establish resting cytosolic Ca2+ concentration and prevent the appearance of pathological signs, paving the way for a possible therapeutic approach against Brody disease. Full article
(This article belongs to the Special Issue Novel Molecular Approaches to Skeletal Muscle Disease and Disuse 2.0)
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20 pages, 1828 KiB  
Article
Nemaline Myopathy in Brazilian Patients: Molecular and Clinical Characterization
by Juliana Gurgel-Giannetti, Lucas Santos Souza, Guilherme L. Yamamoto, Marina Belisario, Monize Lazar, Wilson Campos, Rita de Cassia M. Pavanello, Mayana Zatz, Umbertina Reed, Edmar Zanoteli, Acary Bulle Oliveira, Vilma-Lotta Lehtokari, Erasmo B. Casella, Marcela C. Machado-Costa, Carina Wallgren-Pettersson, Nigel G. Laing, Vincenzo Nigro and Mariz Vainzof
Int. J. Mol. Sci. 2022, 23(19), 11995; https://doi.org/10.3390/ijms231911995 - 9 Oct 2022
Cited by 3 | Viewed by 3326
Abstract
Nemaline myopathy (NM), a structural congenital myopathy, presents a significant clinical and genetic heterogeneity. Here, we compiled molecular and clinical data of 30 Brazilian patients from 25 unrelated families. Next-generation sequencing was able to genetically classify all patients: sixteen families (64%) with mutation [...] Read more.
Nemaline myopathy (NM), a structural congenital myopathy, presents a significant clinical and genetic heterogeneity. Here, we compiled molecular and clinical data of 30 Brazilian patients from 25 unrelated families. Next-generation sequencing was able to genetically classify all patients: sixteen families (64%) with mutation in NEB, five (20%) in ACTA1, two (8%) in KLHL40, and one in TPM2 (4%) and TPM3 (4%). In the NEB-related families, 25 different variants, 11 of them novel, were identified; splice site (10/25) and frame shift (9/25) mutations were the most common. Mutation c.24579 G>C was recurrent in three unrelated patients from the same region, suggesting a common ancestor. Clinically, the “typical” form was the more frequent and caused by mutations in the different NM genes. Phenotypic heterogeneity was observed among patients with mutations in the same gene. Respiratory involvement was very common and often out of proportion with limb weakness. Muscle MRI patterns showed variability within the forms and genes, which was related to the severity of the weakness. Considering the high frequency of NEB mutations and the complexity of this gene, NGS tools should be combined with CNV identification, especially in patients with a likely non-identified second mutation. Full article
(This article belongs to the Special Issue Novel Molecular Approaches to Skeletal Muscle Disease and Disuse 2.0)
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Review

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18 pages, 2699 KiB  
Review
Genes Whose Gain or Loss of Function Changes Type 1, 2A, 2X, or 2B Muscle Fibre Proportions in Mice—A Systematic Review
by Gabryela Kuhnen, Tiago Guedes Russomanno, Marta Murgia, Nicolas J. Pillon, Martin Schönfelder and Henning Wackerhage
Int. J. Mol. Sci. 2022, 23(21), 12933; https://doi.org/10.3390/ijms232112933 - 26 Oct 2022
Cited by 3 | Viewed by 3564
Abstract
Adult skeletal muscle fibres are classified as type 1, 2A, 2X, and 2B. These classifications are based on the expression of the dominant myosin heavy chain isoform. Muscle fibre-specific gene expression and proportions of muscle fibre types change during development and in response [...] Read more.
Adult skeletal muscle fibres are classified as type 1, 2A, 2X, and 2B. These classifications are based on the expression of the dominant myosin heavy chain isoform. Muscle fibre-specific gene expression and proportions of muscle fibre types change during development and in response to exercise, chronic electrical stimulation, or inactivity. To identify genes whose gain or loss-of-function alters type 1, 2A, 2X, or 2B muscle fibre proportions in mice, we conducted a systematic review of transgenic mouse studies. The systematic review was conducted in accordance with the 2009 PRISMA guidelines and the PICO framework. We identified 25 “muscle fibre genes” (Akirin1, Bdkrb2, Bdnf, Camk4, Ccnd3, Cpt1a, Epas1, Esrrg, Foxj3, Foxo1, Il15, Mapk12, Mstn, Myod1, Ncor1, Nfatc1, Nol3, Ppargc1a, Ppargc1b, Sirt1, Sirt3, Thra, Thrb, Trib3, and Vgll2) whose gain or loss-of-function significantly changes type 1, 2A, 2X or 2B muscle fibre proportions in mice. The fact that 15 of the 25 muscle fibre genes are transcriptional regulators suggests that muscle fibre-specific gene expression is primarily regulated transcriptionally. A reanalysis of existing datasets revealed that the expression of Ppargc1a and Vgll2 increases and Mstn decreases after exercise, respectively. This suggests that these genes help to regulate the muscle fibre adaptation to exercise. Finally, there are many known DNA sequence variants of muscle fibre genes. It seems likely that such DNA sequence variants contribute to the large variation of muscle fibre type proportions in the human population. Full article
(This article belongs to the Special Issue Novel Molecular Approaches to Skeletal Muscle Disease and Disuse 2.0)
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