Differential Expression of Genes Involved in the Degeneration and Regeneration Pathways in Mouse Models for Muscular Dystrophies

Onofre-Oliveira, P.C.G.; Santos, André L. F.; Martins, Pedro Pablo Sampaio; Ayub-Guerrieri, D.; Vainzof, Mariz

doi:10.1007/s12017-012-8172-3

Cited by 31 publications

(24 citation statements)

References 34 publications

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“…Once the signaling from the primary MRFs (Myf5 and MyoD) has taken place, the secondary MRFs (myogenin and Mrf4) act to complete the process of muscle regeneration. Myogenin expression is essential in signaling the differentiation of satellite cells into myoblasts and fusion into myotubes 31 , and Mrf4 is then involved in signaling the maturation of the myotubes 32 . Following 24 hours of treatment, DOX promoted an upregulation of Myf5 and MyoD in the SOL which suggests that this myotoxic insult of DOX stimulated signaling for repair in this type I muscle.…”

Section: Discussionmentioning

confidence: 99%

Effects of endurance exercise and doxorubicin on skeletal muscle myogenic regulatory factor expression

Hydock¹

2017

MLTJ

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SummaryBackground: The skeletal muscle toxicity that accompanies the chemotherapy drug doxorubicin (DOX) may lead to cancer patient weakness and fatigue. This myotoxicity involves myogenic regulatory factor (MRF) disruption which alters muscle integrity and regeneration. Endurance exercise enhances MRF expression and thereby may mitigate DOX-induced MRF disruptions. This study examined the effects of endurance training and DOX treatment on myogenic regulatory factor (MRF) expression. Methods: Male rats were exercise trained (EXER) or remained sedentary (SED) for two weeks. EXER and SED then received either DOX (15 mg/kg) or saline (SAL). Soleus, extensor digitorum longus (EDL), and diaphragm were excised 24 hours post injection, and MRF expression was analyzed. Results: Significant Myf5 drug and activity effects were observed in the soleus with EXER+DOX expressing higher Myf5 than SED+DOX. A significant drug effect was detected in soleus MyoD, and a significant activity effect was detected in soleus Mrf4. No main effects or interactions were observed in the EDL, but in the diaphragm, a significant activity effect was observed for Myf5 with EXER+DOX expressing higher levels than SED+DOX. Conclusion: Doxorubicin treatment increased soleus MRFs and exercise boosted MRF response in soleus and diaphragm suggesting that exercise may enhance regenerative signaling with DOX treatment. Level of evidence: I b, individual randomized controlled trial.

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Section: Discussionmentioning

confidence: 99%

Effects of endurance exercise and doxorubicin on skeletal muscle myogenic regulatory factor expression

Hydock¹

2017

MLTJ

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“…TGFβ expression is increased in human DMD muscle and in the mdx mouse [40, 41]. Increased TGFβ expression is associated with excessive matrix accumulation in a wide-variety of diseases, such as liver cirrhosis and cardiac fibrosis [42].…”

Section: Modifiers Of Muscular Dystrophymentioning

confidence: 99%

Genetic Modifiers for Neuromuscular Diseases

Lamar

McNally

2014

Journal of Neuromuscular Diseases

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Neuromuscular diseases, which encompass disorders that affect muscle and its innervation, are highly heritable. Genetic diagnosis now frequently pinpoints the primary mutation responsible for a given neuromuscular disease. However, the results from genetic testing indicate that neuromuscular disease phenotypes may vary widely, even in individuals with the same primary disease-causing mutation. Clinical variability arises from both genetic and environmental factors. Genetic modifiers can now be identified using candidate gene as well as genomic approaches. The presence of genetic modifiers for neuromuscular disease helps define the clinical outcome and also highlights pathways of potential therapeutic utility. Herein, we will focus on single gene neuromuscular disorders, including muscular dystrophy, spinal muscular atrophy, and amyotrophic lateral sclerosis, and the methods that have been used to identify modifier genes. Animal models have been an invaluable resource for modifier gene discovery and subsequent mechanistic studies. Some modifiers, identified using animal models, have successfully translated to the human counterpart. Furthermore, in a few instances, modifier gene discovery has repetitively uncovered the same pathway, such as TGFβ signaling in muscular dystrophy, further emphasizing the relevance of that pathway. Knowledge of genetic factors that influence disease can have direct clinical applications for prognosis and predicted outcome.

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Section: Mimicking Human Muscle Pathologymentioning

confidence: 99%

“…However, these so-called revertant fibres are in a too small minority to alleviate the pathology of the dystrophin-deficiency. Exhaustion of the satellite cell pool due to degeneration and regeneration cycles is thought to critically contribute to the disease [10,11].BMD is also caused by mutations in the dystrophin gene, but myofibrils retain a truncated and low-active form of the dystrophin protein, consequently the symptoms appear with a later, and much slower rate of progression [12,13]. Both BMD and DMD patients can show different degrees of cognitive damage, indicating that brain function is compromised.…”

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confidence: 99%

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Mononucleated Cells to Regenerate Skeletal Muscle Syncytial Tissues

Ceccarelli¹

2012

J Stem Cell Res Ther

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Skeletal muscle is one of the most plastic tissues of vertebrates since it may able upon exercises to double in size due to a physiological hypertrophy. Despite the fact that it is mainly a syncytial tissue, it contains a relevant number of mononucleated cells that can be involved in its homeostasis and repair. Although the mononuclear cell types with the highest myogenic potential are the satellite cells located underneath the basal lamina of muscle fibres, other interstitial cells have been shown to contribute to muscle regeneration.Adding complexity to this scenario is the fact that several authors revealed myogenic potential in pluripotent stem cells, which can be generated from patient somatic cells and eventually manipulated to correct the genetic defect.Notwithstanding the copiousness of myogenic cell types, their use in ex vivo cell therapies for muscular degenerative diseases is still questionable. However, new discovers on their biological properties have advanced our comprehension in handling myogenic stem cells significantly.In this review, we will focus on the myogenic potential of multi-and pluri-potent stem cells and their use in preclinical and clinical studies. New insights from direct reprogramming and epigenetic signalling to generate myogenic stem cells are also considered. Keywords: Stem cells; Skeletal muscle; Regenerative medicine Mimicking Human Muscle PathologyMuscular dystrophies (MDs) are a group of muscle diseases that affect the musculoskeletal system and locomotion [1][2][3][4][5]. MDs are characterized by defects in muscle proteins, determining progressive death of muscle cells and tissue [2,3]. There are several forms of MDs, including the Duchenne muscular dystrophy (DMD), the Becker muscular dystrophy (BMD) and some forms of limb-girdle muscular dystrophy (LGMD).DMD is the most severe syndrome and it is caused by mutations in the dystrophin gene located on the human X chromosome, with an inheritance pattern of 3 cases per 10000 live male births [5][6][7]. Satellite cells are localized underneath the basal lamina of terminally differentiated muscle fibres and in response to injury, they proliferate, fuse and give rise to regenerated muscle. Unfortunately, genetic mutations responsible for DMD are also present in satellite cells. Hence, the ability to restore normal muscle function remains obstructed. In DMD patients a small number of muscle fibres are able to produce functional dystrophin, mostly due to secondary mutations in myogenic precursor cells, which restore the reading frame [8,9]. However, these so-called revertant fibres are in a too small minority to alleviate the pathology of the dystrophin-deficiency. Exhaustion of the satellite cell pool due to degeneration and regeneration cycles is thought to critically contribute to the disease [10,11].BMD is also caused by mutations in the dystrophin gene, but myofibrils retain a truncated and low-active form of the dystrophin protein, consequently the symptoms appear with a later, and much slower rate of progression [12...

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Differential Expression of Genes Involved in the Degeneration and Regeneration Pathways in Mouse Models for Muscular Dystrophies

Cited by 31 publications

References 34 publications

Effects of endurance exercise and doxorubicin on skeletal muscle myogenic regulatory factor expression

Effects of endurance exercise and doxorubicin on skeletal muscle myogenic regulatory factor expression

Genetic Modifiers for Neuromuscular Diseases

Mononucleated Cells to Regenerate Skeletal Muscle Syncytial Tissues

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