Metabolic Functions of Myostatin and GDF11

McPherron, Alexandra C.

doi:10.2174/187152210793663810

Cited by 109 publications

(113 citation statements)

References 136 publications

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“…At baseline, deceased patients had a lower body mass index (24 kg/m 2 vs. 25 kg/m 2 , P = 0.026) and had lost more body weight (5.4% vs. 2.4%, P = 0.019) than alive patients. Moreover, deceased patients had more severe anorexia (SNAQ score: deceased vs. alive patients: 146, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 vs. 168, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20; P = 0.005), more symptoms (QLQ‐C30: deceased vs. alive patients: 33 2–66 vs. 15 6–69 ; P < 0.0001), a poorer quality of life (QLQ‐C30: deceased vs. alive patients: 58 16–100 vs. 66 0–100 ; P = 0.002) and a lower functional capacity (QLQ‐C30: deceased vs. alive patients: 64 18–97 vs. 82 33–100 ; P < 0.0001 and ECOG; P < 0.0001) than alive patients.…”

Section: Resultsmentioning

confidence: 99%

“…Indeed, the binding of ActA to its muscle ActIIB receptor activates an atrophy gene programme via the phosphorylation of Smad2/3. This receptor is also shared with Myostatin, another TGF‐β superfamily member and a negative growth factor of muscle mass 11. In another hand, circulating levels of ActA have been reported to be increased in animal models of cancer cachexia 12.…”

Section: Introductionmentioning

confidence: 99%

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Circulating Activin A predicts survival in cancer patients

Loumaye

Barsy

Nachit

et al. 2017

J cachexia sarcopenia muscle

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BackgroundSeveral experimental evidences pinpoint the possible role of Activin A (ActA) as a driver of cancer cachexia. Supporting this hypothesis, we showed recently that human cancer cachexia is associated with high ActA levels. Moreover, ActA levels were correlated with body weight loss and skeletal muscle density, two prognostic factors in cancer patients. Our goal was therefore to investigate the value of ActA to predict survival in cancer patients.MethodsPatients with colorectal or lung cancer were prospectively enrolled at the time of diagnosis or relapse between January 2012 and March 2014. At baseline, patients had clinical, nutritional, and functional assessment. Body composition and skeletal muscle density were measured by CT scan, and plasma ActA concentrations were determined. Overall survival (OS) was analysed since inclusion to 24 months later.ResultsSurvival data were available for 149 patients out of 152. Patients with high ActA (≥408 pg/mL) had lower OS than those with low levels, regardless the type of cancer (OS in colorectal cancer, 50% vs. 79%, P < 0.05; and in lung cancer, 27% vs. 67%, P = 0.001). The multivariable analysis confirmed the prognostic value of ActA independently of tumour stage or inflammatory markers, particularly in lung cancer. Low muscularity was also an independent prognostic factor.ConclusionsOur study demonstrates that high ActA level is an independent prognosis factor of survival in cancer patients. More than a basic marker of the severity of the neoplastic disease or of the inflammatory process, ActA seems to influence survival by contributing to the development of cachexia and loss of skeletal muscle mass.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Circulating Activin A predicts survival in cancer patients

Loumaye

Barsy

Nachit

et al. 2017

J cachexia sarcopenia muscle

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“…This gene had been studied predominantly for its role in organs such as pancreas, intestine, kidney, skeletal muscle, and developing nervous system. Knockout gdf112/2 mice develop skeletal and gut abnormalities [67]. A role for this gene in human erythropoiesis was found indirectly and serendipitously.…”

Section: Activin Receptor Ligand Trapsmentioning

confidence: 99%

Thalassemia 2016: Modern medicine battles an ancient disease

Rund

2015

American J Hematol

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Thalassemia was first clinically described nearly a century ago and treatment of this widespread genetic disease has greatly advanced during this period. DNA‐based diagnosis elucidated the molecular basis of the disease and clarified the variable clinical picture. It also paved the way for modern methods of carrier identification and prevention via DNA‐based prenatal diagnosis. Every aspect of supportive care, including safer blood supply, more regular transfusions, specific monitoring of iron overload, parenteral and oral chelation, and other therapies, has prolonged life and improved the quality of life of these patients. Significant advances have also been made in allogenic bone marrow transplantation, the only curative therapy. Recently, there has been a rejuvenated interest in studying thalassemia at the basic science level, leading to the discovery of previously unknown mechanisms leading to anemia and enabling the development of novel therapies. These will potentially improve the treatment of, and possibly cure the disease. Pathways involving activin receptors, heat shock proteins, JAK2 inhibitors and macrophage targeted therapy, among others, are being studied or are currently in clinical trials for treating thalassemia. Novel types of genetic therapies are in use or under investigation. In addition to the challenges of treating each individual patient, the longer survival of thalassemia patients has raised considerations regarding worldwide control of thalassemia, since prevention is not universally implemented. This review will trace a number of the original medical milestones of thalassemia diagnosis and treatment, as well as some of the most recent developments which may lead to innovative therapeutic modalities. Am. J. Hematol. 91:15–21, 2016. © 2015 Wiley Periodicals, Inc.

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“…Besides the increased muscularity, the myostatin knockout mice also have reduced body fat with increasing age and are also protected against obesity triggered in genetic models (55). Furthermore, these mice have greater sensitivity for insulin, which might render myostatin an interesting target for treatment of insulin resistance that typically occurs in type II diabetes (52,93). However, currently, it cannot be discerned whether the favorable metabolic effects in myostatin knockout mice were the consequence of reduced myostatin or occur secondarily to increased muscle mass (52).…”

Section: Biology and Function Of Myostatinmentioning

confidence: 99%

“…Furthermore, these mice have greater sensitivity for insulin, which might render myostatin an interesting target for treatment of insulin resistance that typically occurs in type II diabetes (52,93). However, currently, it cannot be discerned whether the favorable metabolic effects in myostatin knockout mice were the consequence of reduced myostatin or occur secondarily to increased muscle mass (52). Overproduction of myostatin in implanted CHO tumor cells induced whole body cachexia, with reduced body weight (approximately Ϫ30%) and muscle weights (approximately Ϫ50%) and with loss of retroperitoneal fat (98).…”

Section: Biology and Function Of Myostatinmentioning

confidence: 99%

Myostatin from the heart: local and systemic actions in cardiac failure and muscle wasting

Breitbart

Auger‐Messier

Molkentin

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

104

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A significant proportion of heart failure patients develop skeletal muscle wasting and cardiac cachexia, which is associated with a very poor prognosis. Recently, myostatin, a cytokine from the transforming growth factor-β (TGF-β) family and a known strong inhibitor of skeletal muscle growth, has been identified as a direct mediator of skeletal muscle atrophy in mice with heart failure. Myostatin is mainly expressed in skeletal muscle, although basal expression is also detectable in heart and adipose tissue. During pathological loading of the heart, the myocardium produces and secretes myostatin into the circulation where it inhibits skeletal muscle growth. Thus, genetic elimination of myostatin from the heart reduces skeletal muscle atrophy in mice with heart failure, whereas transgenic overexpression of myostatin in the heart is capable of inducing muscle wasting. In addition to its endocrine action on skeletal muscle, cardiac myostatin production also modestly inhibits cardiomyocyte growth under certain circumstances, as well as induces cardiac fibrosis and alterations in ventricular function. Interestingly, heart failure patients show elevated myostatin levels in their serum. To therapeutically influence skeletal muscle wasting, direct inhibition of myostatin was shown to positively impact skeletal muscle mass in heart failure, suggesting a promising strategy for the treatment of cardiac cachexia in the future.

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Metabolic Functions of Myostatin and GDF11

Cited by 109 publications

References 136 publications

Circulating Activin A predicts survival in cancer patients

Circulating Activin A predicts survival in cancer patients

Thalassemia 2016: Modern medicine battles an ancient disease

Myostatin from the heart: local and systemic actions in cardiac failure and muscle wasting

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