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https://www.readbyqxmd.com/read/29161592/tumor-suppressor-inactivation-of-gdf11-occurs-by-precursor-sequestration-in-triple-negative-breast-cancer
#1
Sameer S Bajikar, Chun-Chao Wang, Michael A Borten, Elizabeth J Pereira, Kristen A Atkins, Kevin A Janes
Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous carcinoma in which various tumor-suppressor genes are lost by mutation, deletion, or silencing. Here we report a tumor-suppressive mode of action for growth-differentiation factor 11 (GDF11) and an unusual mechanism of its inactivation in TNBC. GDF11 promotes an epithelial, anti-invasive phenotype in 3D triple-negative cultures and intraductal xenografts by sustaining expression of E-cadherin and inhibitor of differentiation 2 (ID2). Surprisingly, clinical TNBCs retain the GDF11 locus and expression of the protein itself...
November 20, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29121992/a-mouse-anti-myostatin-antibody-increases-muscle-mass-and-improves-muscle-strength-and-contractility-in-the-mdx-mouse-model-of-duchenne-muscular-dystrophy-and-its-humanized-equivalent-domagrozumab-pf-06252616-increases-muscle-volume-in-cynomolgus-monkeys
#2
Michael St Andre, Mark Johnson, Prashant N Bansal, Jeremy Wellen, Andrew Robertson, Alan Opsahl, Peter M Burch, Peter Bialek, Carl Morris, Jane Owens
BACKGROUND: The treatments currently approved for Duchenne muscular dystrophy (DMD), a progressive skeletal muscle wasting disease, address the needs of only a small proportion of patients resulting in an urgent need for therapies that benefit all patients regardless of the underlying mutation. Myostatin is a member of the transforming growth factor-β (TGF-β) family of ligands and is a negative regulator of skeletal muscle mass. Loss of myostatin has been shown to increase muscle mass and improve muscle function in both normal and dystrophic mice...
November 9, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/29113418/role-of-growth-differentiation-factor-11-in-development-physiology-and-disease
#3
REVIEW
Yonghui Zhang, Yong Wei, Dan Liu, Feng Liu, Xiaoshan Li, Lianhong Pan, Yi Pang, Dilong Chen
Growth differentiation factor (GDF11) is a member of TGF-β/BMP superfamily that activates Smad and non-Smad signaling pathways and regulates expression of its target nuclear genes. Since its discovery in 1999, studies have shown the involvement of GDF11 in normal physiological processes, such as embryonic development and erythropoiesis, as well as in the pathophysiology of aging, cardiovascular disease, diabetes mellitus, and cancer. In addition, there are contradictory reports regarding the role of GDF11 in aging, cardiovascular disease, diabetes mellitus, osteogenesis, skeletal muscle development, and neurogenesis...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29109273/blockade-of-activin-type-ii-receptors-with-a-dual-anti-actriia-iib-antibody-is-critical-to-promote-maximal-skeletal-muscle-hypertrophy
#4
Frederic Morvan, Jean-Michel Rondeau, Chao Zou, Giulia Minetti, Clemens Scheufler, Meike Scharenberg, Carsten Jacobi, Pascale Brebbia, Veronique Ritter, Gauthier Toussaint, Claudia Koelbing, Xavier Leber, Alain Schilb, Florian Witte, Sylvie Lehmann, Elke Koch, Sabine Geisse, David J Glass, Estelle Lach-Trifilieff
The TGF-β family ligands myostatin, GDF11, and activins are negative regulators of skeletal muscle mass, which have been reported to primarily signal via the ActRIIB receptor on skeletal muscle and thereby induce muscle wasting described as cachexia. Use of a soluble ActRIIB-Fc "trap," to block myostatin pathway signaling in normal or cachectic mice leads to hypertrophy or prevention of muscle loss, perhaps suggesting that the ActRIIB receptor is primarily responsible for muscle growth regulation. Genetic evidence demonstrates however that both ActRIIB- and ActRIIA-deficient mice display a hypertrophic phenotype...
November 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29046533/anatomical-integration-of-the-sacral-hindlimb-unit-coordinated-by-gdf11-underlies-variation-in-hindlimb-positioning-in-tetrapods
#5
Yoshiyuki Matsubara, Tatsuya Hirasawa, Shiro Egawa, Ayumi Hattori, Takaya Suganuma, Yuhei Kohara, Tatsuya Nagai, Koji Tamura, Shigeru Kuratani, Atsushi Kuroiwa, Takayuki Suzuki
Elucidating how body parts from different primordia are integrated during development is essential for understanding the nature of morphological evolution. In tetrapod evolution, while the position of the hindlimb has diversified along with the vertebral formula, the mechanism responsible for this coordination has not been well understood. However, this synchronization suggests the presence of an evolutionarily conserved developmental mechanism that coordinates the positioning of the hindlimb skeleton derived from the lateral plate mesoderm with that of the sacral vertebrae derived from the somites...
September 2017: Nature Ecology & Evolution
https://www.readbyqxmd.com/read/28955765/identification-of-ligand-selective-peptidic-actriib-antagonists-using-phage-display-technology
#6
Kotaro Sakamoto, Yoko Kanematsu-Yamaki, Yusuke Kamada, Masahiro Oka, Toshiyuki Ohnishi, Masanori Miwa, Taiji Asami, Hiroshi Inooka
ActRIIB (activin receptor type-2B) is an activin receptor subtype constitutively expressed in the whole body, playing a role in cellular proliferation, differentiation, and metabolism. For its various physiological activities, ActRIIB interacts with activin and multiple other ligands including myostatin (MSTN), growth differentiation factor 11 (GDF11), and bone morphogenetic protein 9 (BMP9). Notably, the protein-protein interaction (PPI) between ActRIIB and MSTN negatively controls muscular development. Therefore, this PPI has been targeted for effective treatment of muscle degenerative diseases such as muscular dystrophy and sarcopenia...
September 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28938532/modulation-of-gdf11-expression-and-synaptic-plasticity-by-age-and-training
#7
Emanuela De Domenico, Giovanna D'Arcangelo, Isabella Faraoni, Mattia Palmieri, Virginia Tancredi, Grazia Graziani, Paola Grimaldi, Lucio Tentori
The Growth Differentiation Factor 11 (GDF11) has been controversially involved in the aging/rejuvenation process. To clarify whether GDF11 is differently expressed during aging, we have evaluated GDF11 levels in skeletal muscles and hippocampi of young and old mice, sedentary or subjected to a 12-weeks triweekly training protocol. The results of real-time PCR and Western blot analyses indicate that skeletal muscles of sedentary old mice express higher levels of GDF11 compared to young animals (p < 0.05)...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912874/dietary-vitamin-b6-modulates-the-gene-expression-of-myokines-nrf2-related-factors-myogenin-and-hsp60-in-the-skeletal-muscle-of-rats
#8
Sofya Suidasari, Shinji Uragami, Noriyuki Yanaka, Norihisa Kato
Previous studies have suggested that vitamin B6 is an ergogenic factor. However, the role of dietary vitamin B6 in skeletal muscle has not been widely researched. The aim of the present study was to investigate the effects of dietary vitamin B6 on the gene expression of 19 myokines, 14 nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated factors, 8 myogenesis-related factors and 4 heat shock proteins (HSPs), which may serve important roles in skeletal muscles. Rats were fed a diet containing 1 (marginal vitamin B6 deficiency), 7 (recommended dietary level) or 35 mg/kg of pyridoxine (PN) HCl/ for 6 weeks...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28829672/growth-differentiation-factor-11-does-not-mitigate-the-lethal-effects-of-total-abdominal-irradiation
#9
Sara Duhachek-Muggy, Kruttika Bhat, Erina Vlashi, Frank Pajonk
Total-body exposure to radiation causes widespread tissue injury. Damage to the hematopoietic and intestinal stem cell compartments is particularly lethal and mitigators of this damage are critical in providing effective treatment. Parabiosis radiation experiments, in which the vasculatures of two rodents are anastomosed prior to irradiation of one of the animals, have shown that there is a circulating factor that protects mice from radiation-induced intestinal death. Recently reported studies have suggested that growth differentiation factor 11 (GDF11) is responsible for the rejuvenation of stem cells observed in parabiosis experiments involving aging mice...
November 2017: Radiation Research
https://www.readbyqxmd.com/read/28802278/gdf11-a-fountain-of-youth-for-the-ageing-copd-lung
#10
EDITORIAL
Ma'en Obeidat, Don D Sin
No abstract text is available yet for this article.
August 11, 2017: Thorax
https://www.readbyqxmd.com/read/28721633/erratum-to-exogenous-gdf11-induces-cardiac-and-skeletal-muscle-dysfunction-and-wasting
#11
Teresa A Zimmers, Yanlin Jiang, Meijing Wang, Tiffany W Liang, Joseph E Rupert, Ernie D Au, Francesco E Marino, Marion E Couch, Leonidas G Koniaris
No abstract text is available yet for this article.
September 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28715204/a-prodomain-fragment-from-the-proteolytic-activation-of-growth-differentiation-factor-11-remains-associated-with-the-mature-growth-factor-and-keeps-it-soluble
#12
Blake Pepinsky, Bang-Jian Gong, Yan Gao, Andreas Lehmann, Janine Ferrant, Joseph Amatucci, Yaping Sun, Martin Bush, Thomas Walz, Nels Pederson, Thomas Cameron, Dingyi Wen
Growth differentiation factor 11 (GDF11), a member of the transforming growth factor β (TGF-β) family, plays diverse roles in mammalian development. It is synthesized as a large, inactive precursor protein containing a prodomain, pro-GDF11, and exists as a homodimer. Activation requires two proteolytic processing steps that release the prodomains and transform latent pro-GDF11 into active mature GDF11. In studying proteolytic activation in vitro, we discovered that a 6-kDa prodomain peptide containing residues 60-114, PDP60-114, remained associated with the mature growth factor...
August 22, 2017: Biochemistry
https://www.readbyqxmd.com/read/28701523/lifelong-exercise-but-not-short-term-high-intensity-interval-training-increases-gdf11-a-marker-of-successful-aging-a%C3%A2-preliminary-investigation
#13
Bradley T Elliott, Peter Herbert, Nicholas Sculthorpe, Fergal M Grace, Daniel Stratton, Lawrence D Hayes
Lifelong exercise is associated with regulation of skeletal mass and function, reductions in frailty, and successful aging. Yet, the influence of exercise on myostatin and myostatin-interacting factors is relatively under examined in older males. Therefore, we investigated whether serum total myostatin, free myostatin, follistatin, and growth and differentiation factor 11 (GDF11) were altered following high-intensity interval training (HIIT) in a group of 13 lifelong sedentary (SED; 64 [6] years) and 11 lifelong exercising (LEX; 62 [6] years) older males...
July 2017: Physiological Reports
https://www.readbyqxmd.com/read/28695962/gdf11-smad-signalling-and-cdx-proteins-cooperate-to-activate-the-hoxc8-early-enhancer-in-hepg2-cells
#14
Stephen J Gaunt
Developing anatomy along the head-tail axis of bilaterian embryos is specified, to a large extent, by the overlapping patterns of expression of the Hox genes. Hox gene enhancers respond to a variety of signals in order to regulate these discreet domains of expression. For mouse Hoxc8, the 399bp "early enhancer" plays a major role. Activation of this enhancer is now examined using luciferase expression constructs transfected into HepG2 cells. Constructs are activated by the combined actions of Gdf11/Smad and Cdx protein signalling pathways, both of which are functional in early embryos...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28647906/exogenous-gdf11-induces-cardiac-and-skeletal-muscle-dysfunction-and-wasting
#15
Teresa A Zimmers, Yanling Jiang, Meijing Wang, Tiffany W Liang, Joseph E Rupert, Ernie D Au, Francesco E Marino, Marion E Couch, Leonidas G Koniaris
Growth differentiation factor 11 (GDF11), a TGF-beta superfamily member, is highly homologous to myostatin and essential for embryonic patterning and organogenesis. Reports of GDF11 effects on adult tissues are conflicting, with some describing anti-aging and pro-regenerative activities on the heart and skeletal muscle while others opposite or no effects. Herein, we sought to determine the in vivo cardiac and skeletal muscle effects of excess GDF11. Mice were injected with GDF11 secreting cells, an identical model to that used to initially identify the in vivo effects of myostatin...
July 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28533206/myostatin-like-proteins-regulate-synaptic-function-and-neuronal-morphology
#16
Hrvoje Augustin, Kieran McGourty, Joern R Steinert, Helena M Cochemé, Jennifer Adcott, Melissa Cabecinha, Alec Vincent, Els F Halff, Josef T Kittler, Emmanuel Boucrot, Linda Partridge
Growth factors of the TGFβ superfamily play key roles in regulating neuronal and muscle function. Myostatin (or GDF8) and GDF11 are potent negative regulators of skeletal muscle mass. However, expression of myostatin and its cognate receptors in other tissues, including brain and peripheral nerves, suggests a potential wider biological role. Here, we show that Myoglianin (MYO), the Drosophila homolog of myostatin and GDF11, regulates not only body weight and muscle size, but also inhibits neuromuscular synapse strength and composition in a Smad2-dependent manner...
July 1, 2017: Development
https://www.readbyqxmd.com/read/28508553/a-targeted-proteomic-assay-for-the-measurement-of-plasma-proteoforms-related-to-human-aging-phenotypes
#17
Richard D Semba, Pingbo Zhang, Min Zhu, Elisa Fabbri, Marta Gonzalez-Freire, Ruin Moaddel, Minghui Geng-Spyropoulos, Luigi Ferrucci
Circulating polypeptides and proteins have been implicated in reversing or accelerating aging phenotypes, including growth/differentiation factor 8 (GDF8), GDF11, eotaxin, and oxytocin. These proteoforms, which are defined as the protein products arising from a single gene due to alternative splicing and PTMs, have been challenging to study. Both GDF8 and GDF11 have known antagonists such as follistatin (FST), and WAP, Kazal, immunoglobulin, Kunitz, and NTR domain-containing proteins 1 and 2 (WFIKKN1, WFIKKN2)...
August 2017: Proteomics
https://www.readbyqxmd.com/read/28501597/reciprocal-regulation-between-hepcidin-and-erythropoiesis-and-its-therapeutic-application-in-erythroid-disorders
#18
REVIEW
Caiyi Wang, Zheng Fang, Zesen Zhu, Jing Liu, Huiyong Chen
Iron is required for hemoglobin production, and it plays a key role during erythropoiesis. Systemic iron homeostasis is mainly negatively regulated by the peptide hormone hepcidin, coded by the gene HAMP. Hepcidin excess may cause iron deficiency, iron-restricted erythropoiesis, and anemia. Conversely, hepcidin insufficiency leads to iron overload and oxidative damage in multiple tissues. During regulation of hepcidin synthesis, multiple promoter elements in the HAMP gene respond to variable signaling pathways corresponding to different extracellular situations...
August 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28485800/gdf11-does-not-improve-the-palmitate-induced-insulin-resistance-in-c2c12
#19
Y-Y Jing, D Li, F Wu, L-L Gong, R Li
OBJECTIVE: GDF11 (Growth Differentiation factor 11) has been reported to rejuvenate skeletal muscle, heart and brain in aged mice, and the aged skeletal muscle is closely related to insulin resistance. We wondered whether GDF11 has an effect on skeletal muscle insulin resistance. MATERIALS AND METHODS: High fat diet induced obese mice with insulin resistance were established in vivo. Palmitate-induced insulin resistance in C2C12 myotubes was established in vitro...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28478937/coexpression-of-growth-differentiation-factor-11-and-reactive-oxygen-species-in-metastatic-oral-cancer-and-its-role-in-inducing-the-epithelial-to-mesenchymal-transition
#20
Xiangming Qin, Hai Kuang, Lei Chen, Shanliang Wei, Dahai Yu, Feixin Liang
OBJECTIVES: The aim of this study was to investigate growth differentiation factor 11 (GDF11) and reactive oxygen species (ROS) expression in metastatic oral cancer and explored their roles in inducing epithelial to mesenchymal transition (EMT). STUDY DESIGN: The expression of GDF11, ROS, and EMT-related markers was evaluated in primary tumor tissues from patients with oral squamous cell carcinoma (OSCC). SCC-9 cells, a human tongue carcinoma cell line, were treated with recombinant GDF11...
June 2017: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
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