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Activin A

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https://www.readbyqxmd.com/read/28943409/interleukin-1-%C3%AE-induced-smad2-3-linker-modifications-are-tak1-dependent-and-delay-tgf%C3%AE-signaling-in-primary-human-mesenchymal-stem-cells
#1
Guus G van den Akker, Henk M van Beuningen, Elly L Vitters, Marije I Koenders, Fons A de Loo, Peter L van Lent, Esmeralda N Blaney Davidson, Peter M van der Kraan
BACKGROUND: Chondrogenic differentiation of mesenchymal stem cells (MSC) requires transforming growth factor beta (TGFβ) signaling. TGFβ binds to the type I receptor activin-like kinase (ALK)5 and results in C-terminal SMAD2/3 phosphorylation (pSMAD2/3C). In turn pSMAD2/3C translocates to the nucleus and regulates target gene expression. Inflammatory mediators are known to exert an inhibitory effect on MSC differentiation. In this study we investigated the effect of interleukin 1 β (IL1β) on SMAD2/3 signaling dynamics and post-translational modifications...
September 21, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28940410/mechanisms-of-bone-destruction-in-multiple-myeloma
#2
REVIEW
E Terpos, D Christoulas, M Gavriatopoulou, M A Dimopoulos
Osteolytic bone disease is a frequent complication of multiple myeloma, resulting in skeletal complications that are a significant cause of morbidity and mortality. It is the result of an increased activity of osteoclasts, which is not followed by reactive bone formation by osteoblasts. Recent studies have revealed novel molecules and pathways that are implicated in osteoclast activation and osteoblast inhibition. Among them, the most important include the receptor activator of nuclear factor-kappa B ligand/osteoprotegerin pathway, the macrophage inflammatory proteins and the activin-A that play a crucial role in osteoclast stimulation in myeloma, while the wingless-type (Wnt) signalling inhibitors (sclerostin and dickkopf-1) along with the growth factor independence-1 are considered the most important factors for the osteoblast dysfunction of myeloma patients...
September 21, 2017: European Journal of Cancer Care
https://www.readbyqxmd.com/read/28939526/inhibition-of-the-tgf-%C3%AE-1-smad-signaling-pathway-protects-against-cartilage-injury-and-osteoarthritis-in-a-rat-model
#3
Yong-Jian Wang, Min Shen, Shan Wang, Xin Wen, Xin-Rui Han, Zi-Feng Zhang, Hui Li, Fei Wang, Dong-Mei Wu, Jun Lu, Yuan-Lin Zheng
Transforming growth factor-β1 (TGF-β1) in osteoblastic cells triggers pathological changes observed in osteoarthritis (OA). Thus, we hypothesized that the inhibition of the TGF-β1/Smad signaling pathway could act to protect against cartilage injury in rats with OA. After establishment of rat models induced by papain and L-cysteine, rats were subsequently assigned into the TβRI inhibitors, normal control (NC) and OA model groups. RT-qPCR and western blotting were performed to determine mRNA and protein expressions of TGFβ1, Smad2, Smad3 and Activin receptor-like kinase 5 (ALK5), respectively...
September 19, 2017: Life Sciences
https://www.readbyqxmd.com/read/28938435/the-role-of-sequential-bmp-signaling-in-directing-human-embryonic-stem-cells-to-bipotential-gonadal-cells
#4
Kirsi Sepponen, Karolina Lundin, Katri Knuus, Pia Väyrynen, Taneli Raivio, Juha S Tapanainen, Timo Tuuri
Context: Human gonads arise as a pair of epithelial ridges on the surface of intermediate mesoderm (IM)-derived mesonephros. Toxic environmental factors and mutations in various genes are known to disturb normal gonadal development, but due to a lack of suitable in vitro models, detailed studies characterizing the molecular basis of the observed defects have not been performed. Objective: Our objective was to establish an in vitro method for studying differentiation of bipotential gonadal progenitors using human embryonic stem cells (hESCs), and to investigate the role of bone morphogenetic protein (BMP) in gonadal differentiation...
August 29, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28934877/activin-and-nodal-are-not-suitable-alternatives-to-tgf%C3%AE-for-chondrogenic-differentiation-of-mesenchymal-stem-cells
#5
Laurie M G de Kroon, Esmeralda N Blaney Davidson, Roberto Narcisi, Eric Farrell, Peter M van der Kraan, Gerjo J V M van Osch
Objective Previously, we demonstrated the importance of transforming growth factor-β (TGFβ)-activated SMAD2/3 signaling in chondrogenesis of bone marrow-derived mesenchymal stem cells (BMSCs). However, TGFβ also signals via the SMAD1/5/9 pathway, which is known to induce terminal differentiation of BMSCs. In this study, we investigated whether other SMAD2/3-activating ligands, Activin and Nodal, can induce chondrogenic differentiation of BMSCs without inducing terminal differentiation. Design Activation of SMAD2/3 signaling and chondrogenesis were evaluated in human BMSCs ( N = 3 donors) stimulated with TGFβ, Activin, or Nodal...
October 2017: Cartilage
https://www.readbyqxmd.com/read/28928715/intrinsic-and-regulated-gonadotropin-releasing-hormone-receptor-gene-transcription-in-mammalian-pituitary-gonadotrophs
#6
REVIEW
Marija M Janjic, Stanko S Stojilkovic, Ivana Bjelobaba
The hypothalamic decapeptide gonadotropin-releasing hormone (GnRH), acting via its receptors (GnRHRs) expressed in pituitary gonadotrophs, represents a critical molecule in control of reproductive functions in all vertebrate species. GnRH-activated receptors regulate synthesis of gonadotropins in a frequency-dependent manner. The number of GnRHRs on the plasma membrane determines the responsiveness of gonadotrophs to GnRH and varies in relation to age, sex, and physiological status. This is achieved by a complex control that operates at transcriptional, translational, and posttranslational levels...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28928419/the-histone-deacetylase-sirt6-blocks-myostatin-expression-and-development-of-muscle-atrophy
#7
Sadhana A Samant, Abhinav Kanwal, Vinodkumar B Pillai, Riyue Bao, Mahesh P Gupta
Muscle wasting, also known as cachexia, is associated with many chronic diseases, which worsens prognosis of primary illness leading to enhanced mortality. Molecular basis of this metabolic syndrome is not yet completely understood. SIRT6 is a chromatin-bound member of the sirtuin family, implicated in regulating many cellular processes, ranging from metabolism, DNA repair to aging. SIRT6 knockout (SIRT6-KO) mice display loss of muscle, fat and bone density, typical characteristics of cachexia. Here we report that SIRT6 depletion in cardiac as well as skeletal muscle cells promotes myostatin (Mstn) expression...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28927913/association-of-acvrl1-genetic-polymorphisms-with-arteriovenous-malformations-a-case-control-study-and-meta-analysis
#8
Mingxu Ge, Chigang Du, Zhaona Li, Yingchao Liu, Shangchen Xu, Liyong Zhang, Qi Pang
OBJECTIVE: To investigate the association between polymorphisms in the gene encoding activin receptor-like kinase 1 (ACVRL1) with brain arteriovenous malformations (BAVMs) using a case-control study in a Chinese Han population, followed by a meta-analysis of the published literature. METHODS: This study focused on the genotypic analysis of four single nucleotide polymorphisms (SNPs; rs2071219, rs706819, rs2293094, and rs11169953) in 50 BAVM patients and 120 healthy volunteers attending Provincial Hospital in China...
September 16, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28927503/learning-induces-the-translin-trax-rnase-complex-to-express-activin-receptors-for-persistent-memory
#9
Alan Jung Park, Robbert Havekes, Xiuping Fu, Rolf Hansen, Jennifer C Tudor, Lucia Peixoto, Zhi Li, Yen-Ching Wu, Shane G Poplawski, Jay M Baraban, Ted Abel
Long-lasting forms of synaptic plasticity and memory require de novo protein synthesis. Yet, how learning triggers this process to form memory is unclear. Translin/trax is a candidate to drive this learning-induced memory mechanism by suppressing microRNA-mediated translational silencing at activated synapses. We find that mice lacking translin/trax display defects in synaptic tagging, which requires protein synthesis at activated synapses, and long-term memory. Hippocampal samples harvested from these mice following learning show increases in several disease-related microRNAs targeting the activin A receptor type 1C (ACVR1C), a component of the transforming growth factor-β receptor superfamily...
September 20, 2017: ELife
https://www.readbyqxmd.com/read/28919262/pdgfra-is-not-essential-for-the-derivation-and-maintenance-of-mouse-extraembryonic-endoderm-stem-cell-lines
#10
Jiangwei Lin, Mona Khan, Bolek Zapiec, Peter Mombaerts
Extraembryonic endoderm stem (XEN) cell lines can be derived and maintained in vitro and reflect the primitive endoderm lineage. Platelet-derived growth factor receptor alpha (PDGFRA) is thought to be essential for the derivation and maintenance of mouse XEN cell lines. Here, we have re-evaluated this requirement for PDGFRA. We derived multiple PDGFRA-deficient XEN cell lines from postimplantation and preimplantation embryos of a PDGFRA-GFP knockout strain. We also converted PDGFRA-deficient embryonic stem cell lines into XEN cell lines chemically by transient culturing with retinoic acid and Activin A...
September 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28913617/fingolimod-induces-neuronal-specific-gene-expression-with-potential-neuroprotective-outcomes-in-maturing-neuronal-progenitor-cells-exposed-to-hiv
#11
Rebeca Geffin, Ricardo Martinez, Alicia de Las Pozas, Biju Issac, Micheline McCarthy
Fingolimod (FTY720), a structural analogue of sphingosine, targets sphingosine-1-phosphate receptor signaling and is currently an immunomodulatory therapy for multiple sclerosis. Fingolimod accesses the central nervous system (CNS) where its active metabolite, fingolimod phosphate (FTY720-P), has pleotropic neuroprotective effects in an inflammatory microenvironment. To investigate potential neuronal-specific mechanisms of fingolimod neuroprotection, we cultured the human neuronal progenitor cell line, hNP1, in differentiation medium supplemented with HIV- or Mock-infected supernatants, with or without FTY720-P...
September 14, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28912572/follistatin-n-terminus-differentially-regulates-muscle-size-and-fat-in-vivo
#12
Hui Zheng, Chunping Qiao, Ruhang Tang, Jianbin Li, Karen Bulaklak, Zhenhua Huang, Chunxia Zhao, Yi Dai, Juan Li, Xiao Xiao
Delivery of follistatin (FST) represents a promising strategy for both muscular dystrophies and diabetes, as FST is a robust antagonist of myostatin and activin, which are critical regulators of skeletal muscle and adipose tissues. FST is a multi-domain protein, and deciphering the function of different domains will facilitate novel designs for FST-based therapy. Our study aims to investigate the role of the N-terminal domain (ND) of FST in regulating muscle and fat mass in vivo. Different FST constructs were created and packaged into the adeno-associated viral vector (AAV)...
September 15, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28905498/effect-of-bimagrumab-on-thigh-muscle-volume-and-composition-in-men-with-casting-induced-atrophy
#13
Daniel S Rooks, Didier Laurent, Jens Praestgaard, Scott Rasmussen, Michael Bartlett, László B Tankó
BACKGROUND: Patients experiencing disuse atrophy report acute loss of skeletal muscle mass which subsequently leads to loss of strength and physical capacity. In such patients, especially the elderly, complete recovery remains a challenge even with improved nutrition and resistance exercise. This study aimed to explore the clinical potential of bimagrumab, a human monoclonal antibody targeting the activin type II receptor, for the recovery of skeletal muscle volume from disuse atrophy using an experimental model of lower extremity immobilization...
September 14, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/28904872/treatment-of-renal-anemia-erythropoiesis-stimulating-agents-and-beyond
#14
REVIEW
Patrick Biggar, Gheun-Ho Kim
Anemia, complicating the course of chronic kidney disease, is a significant parameter, whether interpreted as subjective impairment or an objective prognostic marker. Renal anemia is predominantly due to relative erythropoietin (EPO) deficiency. EPO inhibits apoptosis of erythrocyte precursors. Studies using EPO substitution have shown that increasing hemoglobin (Hb) levels up to 10-11 g/dL is associated with clinical improvement. However, it has not been unequivocally proven that further intensification of erythropoiesis stimulating agent (ESA) therapy actually leads to a comprehensive benefit for the patient, especially as ESAs are potentially associated with increased cerebro-cardiovascular events...
September 2017: Kidney Research and Clinical Practice
https://www.readbyqxmd.com/read/28893916/the-role-of-activins-in-hepcidin-regulation-during-malaria
#15
Natasha Spottiswoode, Andrew E Armitage, Andrew R Williams, Alex J Fyfe, Sumi Biswas, Susanne H Hodgson, David Llewellyn, Prateek Choudhary, Simon J Draper, Patrick Duffy, Hal Drakesmith
Epidemiological observations have linked increased host iron with malaria susceptibility, and perturbed iron handling has been hypothesized to contribute to the potentially life threatening anemia that may accompany blood-stage malaria infection. To improve our understanding of these relationships, we examined the pathways involved in regulation of the master controller of iron metabolism, the hormone hepcidin, in malaria infection. We show that hepcidin upregulation in Plasmodium berghei murine malaria infection was accompanied by changes in expression of bone morphogenetic protein (BMP)/sons of mothers against decapentaplegic (SMAD) pathway target genes, a key pathway involved in hepcidin regulation...
September 11, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28883808/grass-carp-follisatin-molecular-cloning-functional-characterization-dopamine-d1-regulation-at-pituitary-level-and-implication-in-growth-hormone-regulation
#16
Roger S K Fung, Bai Jin, Mulan He, Karen W Y Yuen, Anderson O L Wong
Activin is involved in pituitary hormone regulation and its pituitary actions can be nullified by local production of its binding protein follistatin. In our recent study with grass carp, local release of growth hormone (GH) was shown to induce activin expression at pituitary level, which in turn could exert an intrapituitary feedback to inhibit GH synthesis and secretion. To further examine the activin/follistatin system in the carp pituitary, grass carp follistatin was cloned and confirmed to be single-copy gene widely expressed at tissue level...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28871312/alk1-signaling-in-development-and-disease-new-paradigms
#17
REVIEW
Beth L Roman, Andrew P Hinck
Activin A receptor like type 1 (ALK1) is a transmembrane serine/threonine receptor kinase in the transforming growth factor-beta receptor family that is expressed on endothelial cells. Defects in ALK1 signaling cause the autosomal dominant vascular disorder, hereditary hemorrhagic telangiectasia (HHT), which is characterized by development of direct connections between arteries and veins, or arteriovenous malformations (AVMs). Although previous studies have implicated ALK1 in various aspects of sprouting angiogenesis, including tip/stalk cell selection, migration, and proliferation, recent work suggests an intriguing role for ALK1 in transducing a flow-based signal that governs directed endothelial cell migration within patent, perfused vessels...
September 4, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28871189/expression-and-anti-inflammatory-role-of-activin-receptor-interacting-protein-2-in-lipopolysaccharide-activated-macrophages
#18
Qian Wu, Yan Qi, Na Wu, Chunhui Ma, Wenfang Feng, Xueling Cui, Zhonghui Liu
The bacterial endotoxin lipopolysaccharide (LPS), a key pathogenic stimulator, can induce the activation of macrophages. Activin receptor-interacting protein 2 (ARIP2), an intracellular signaling protein, has a wide histological distribution, however, whether ARIP2 is involved in regulation of activation of macrophages was not well characterized. Here, by immunocytochemical staining, we found that ARIP2 protein existed in monocyte-macrophage cell line RAW264.7 cells and peritoneal macrophages of mouse, and ARIP2 expression in RAW264...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28870245/mice-overexpressing-growth-hormone-exhibit-increased-skeletal-muscle-myostatin-and-murf1-with-attenuation-of-muscle-mass
#19
Leslie A Consitt, Alicson Saneda, Gunjan Saxena, Edward O List, John J Kopchick
BACKGROUND: In contrast to the acute effects of growth hormone (GH) on skeletal muscle protein synthesis, long-term GH treatment appears to have negligible effects on muscle mass. Despite this knowledge, little is known regarding the chronic effects of GH on skeletal muscle protein synthesis and atrophy signaling pathways. The purpose of this study was to determine if protein synthesis pathways are attenuated and/or muscle atrophy intracellular signaling pathways are altered in the skeletal muscle of transgenic bovine GH (bGH) mice...
September 4, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28869862/bmp-2-and-bmp-9-binding-specificities-with-alk-3-in-aqueous-solution-with-dynamics
#20
Orkid Coskuner, Vladimir N Uversky
Signal ligands of the transforming growth factor-β (TGF-β) superfamily include the bone morphogenetic proteins (BMPs). BMPs bind to type I and type II serine-threonine kinase receptors and trigger the transphosphorylation cascade, wherein the active type II receptor phosphorylates the inactive type I receptor. This process further activates the cytoplasmic effectors of the pathway, such as SMAD proteins, which are homologs of both the Drosophila protein MAD (mothers against decapentaplegic) and the Caenorhabditis elegans protein SMA (small body size)...
August 9, 2017: Journal of Molecular Graphics & Modelling
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