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Activin A

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https://www.readbyqxmd.com/read/27909336/c-terminal-truncated-hbv-x-promotes-hepato-oncogenesis-through-inhibition-of-tumor-suppressive-%C3%AE-catenin-bambi-signaling
#1
Seok Lee, Mi-Jin Lee, Jun Zhang, Goung-Ran Yu, Dae-Ghon Kim
C-terminal-truncated hepatitis B virus (HBV) X (HBx) (ctHBX) is frequently detected in hepatocellular carcinoma (HCC) through HBV integration into the host genome. However, the molecular mechanisms underlying ctHBx-associated oncogenic signaling have not yet been clarified. To elucidate the biological role of ctHBx in hepato-oncogenesis, we functionally analyzed ctHBx-mediated regulation of the activin membrane-bound inhibitor bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) through transforming growth factor-β (TGF-β) or β-catenin (CTNNB1) in HCC cells and in an animal model, and we compared its role to that of the full-length HBx protein...
December 2, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27908413/trace-element-and-cytokine-concentrations-in-patients-with-fibrodysplasia-ossificans-progressiva-fop-a-case-control-study
#2
Laura Hildebrand, Timo Gaber, Peter Kühnen, Rolf Morhart, Heinz Unterbörsch, Lutz Schomburg, Petra Seemann
Fibrodysplasia Ossificans Progressiva (FOP) is a rare inherited disease characterized by progressive heterotopic ossification. Disease onset, severity and symptoms vary between FOP patients, as does the frequency and activity of so-called flare-ups, during which tendons, ligaments, muscle and soft tissue are replaced by bone. Traumata, infections or other stressors are known inducers of flare-ups, and the hormone Activin A may be involved in disease activity; however, reliable biomarkers for FOP activity are missing, and the basal trace element and inflammatory state of patients are unknown...
January 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/27906170/generating-high-purity-cardiac-and-endothelial-derivatives-from-patterned-mesoderm-using-human-pluripotent-stem-cells
#3
Nathan J Palpant, Lil Pabon, Clayton E Friedman, Meredith Roberts, Brandon Hadland, Rebecca J Zaunbrecher, Irwin Bernstein, Ying Zheng, Charles E Murry
Human pluripotent stem cells (hPSCs) provide a valuable model for the study of human development and a means to generate a scalable source of cells for therapeutic applications. This protocol specifies cell fate efficiently into cardiac and endothelial lineages from hPSCs. The protocol takes 2 weeks to complete and requires experience in hPSC culture and differentiation techniques. Building on lessons taken from early development, this monolayer-directed differentiation protocol uses different concentrations of activin A and bone morphogenetic protein 4 (BMP4) to polarize cells into mesodermal subtypes that reflect mid-primitive-streak cardiogenic mesoderm and posterior-primitive-streak hemogenic mesoderm...
January 2017: Nature Protocols
https://www.readbyqxmd.com/read/27906072/actrii-blockade-protects-mice-from-cancer-cachexia-and-prolongs-survival-in-the-presence-of-anti-cancer-treatments
#4
Shinji Hatakeyama, Serge Summermatter, Marie Jourdain, Stefan Melly, Giulia C Minetti, Estelle Lach-Trifilieff
BACKGROUND: Cachexia affects the majority of patients with advanced cancer and is associated with reduced treatment tolerance, response to therapy, quality of life, and life expectancy. Cachectic patients with advanced cancer often receive anti-cancer therapies against their specific cancer type as a standard of care, and whether specific ActRII inhibition is efficacious when combined with anti-cancer agents has not been elucidated yet. METHODS: In this study, we evaluated interactions between ActRII blockade and anti-cancer agents in CT-26 mouse colon cancer-induced cachexia model...
July 26, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906065/dystrophin-deficient-dogs-with-reduced-myostatin-have-unequal-muscle-growth-and-greater-joint-contractures
#5
Joe N Kornegay, Daniel J Bogan, Janet R Bogan, Jennifer L Dow, Jiahui Wang, Zheng Fan, Naili Liu, Leigh C Warsing, Robert W Grange, Mihye Ahn, Cynthia J Balog-Alvarez, Steven W Cotten, Monte S Willis, Candice Brinkmeyer-Langford, Hongtu Zhu, Joe Palandra, Carl A Morris, Martin A Styner, Kathryn R Wagner
BACKGROUND: Myostatin (Mstn) is a negative regulator of muscle growth whose inhibition promotes muscle growth and regeneration. Dystrophin-deficient mdx mice in which myostatin is knocked out or inhibited postnatally have a less severe phenotype with greater total mass and strength and less fibrosis and fatty replacement of muscles than mdx mice with wild-type myostatin expression. Dogs with golden retriever muscular dystrophy (GRMD) have previously been noted to have increased muscle mass and reduced fibrosis after systemic postnatal myostatin inhibition...
April 4, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906049/smad-dependent-mechanisms-of-inflammatory-bone-destruction
#6
REVIEW
Michelle Fennen, Thomas Pap, Berno Dankbar
Homeostatic bone remodelling becomes disturbed in a variety of pathologic conditions that affect the skeleton, including inflammatory diseases. Rheumatoid arthritis is the prototype of an inflammatory arthritis characterised by chronic inflammation, progressive cartilage destruction and focal bone erosions and is a prime example for a disease with disturbed bone homeostasis. The inflammatory milieu favours the recruitment and activation of osteoclasts, which have been found to be the cells that are primarily responsible for bone erosions in many animal models of inflammatory arthritis...
December 1, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27904762/activin-receptor-like-kinases-a-diverse-family-playing-an-important-role-in-cancer
#7
REVIEW
Holli A Loomans, Claudia D Andl
The role and function of the members of the TGFβ superfamily has been a substantial area of research focus for the last several decades. During that time, it has become apparent that aberrations in TGFβ family signaling, whether through the BMP, Activin, or TGFβ arms of the pathway, can result in tumorigenesis or contribute to its progression. Downstream signaling regulates cellular growth under normal physiological conditions yet induces diverse processes during carcinogenesis, ranging from epithelial- to-mesenchymal transition to cell migration and invasion to angiogenesis...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27898753/-oncogen-dependent-regulation-of-the-migration-and-proliferation-of-human-tumor-cells
#8
Tamás M Garay
The high mortality of solid tumors can be attributed to their invasive and metastatic potential that is based on their migration and proliferation. Importantly, growth factor receptor (GF) signaling pathways regulating proliferation and migration are often affected by oncogenic mutations and are important targets for antitumor therapy. We found positive correlation between migration and proliferation in melanoma and lung cancer cells using videomicroscopy, not supporting the "go or grow" hypothesis. Furthermore, the invasion into collagen I matrices from brain tumor spheroids was not impaired upon the inhibition of proliferation...
November 29, 2016: Magyar Onkologia
https://www.readbyqxmd.com/read/27897407/activin-a-induces-skeletal-muscle-catabolism-via-p38%C3%AE-mitogen-activated-protein-kinase
#9
Hui Ding, Guohua Zhang, Ka Wai Thomas Sin, Zhelong Liu, Ren-Kuo Lin, Min Li, Yi-Ping Li
BACKGROUND: Activation of type IIB activin receptor (ActRIIB) in skeletal muscle leads to muscle atrophy because of increased muscle protein degradation. However, the intracellular signalling mechanism that mediates ActRIIB-activated muscle catabolism is poorly defined. METHODS: We investigated the role of p38β mitogen-activated protein kinases (MAPK) in mediating ActRIIB ligand activin A-activated muscle catabolic pathways in C2C12 myotubes and in mice with perturbation of this kinase pharmacologically and genetically...
September 16, 2016: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/27897192/pi3-kinase-inhibition-improves-vascular-malformations-in-mouse-models-of-hereditary-haemorrhagic-telangiectasia
#10
Roxana Ola, Alexandre Dubrac, Jinah Han, Feng Zhang, Jennifer S Fang, Bruno Larrivée, Monica Lee, Ana A Urarte, Jan R Kraehling, Gael Genet, Karen K Hirschi, William C Sessa, Francesc V Canals, Mariona Graupera, Minhong Yan, Lawrence H Young, Paul S Oh, Anne Eichmann
Activin receptor-like kinase 1 (ALK1) is an endothelial serine-threonine kinase receptor for bone morphogenetic proteins (BMPs) 9 and 10. Inactivating mutations in the ALK1 gene cause hereditary haemorrhagic telangiectasia type 2 (HHT2), a disabling disease characterized by excessive angiogenesis with arteriovenous malformations (AVMs). Here we show that inducible, endothelial-specific homozygous Alk1 inactivation and BMP9/10 ligand blockade both lead to AVM formation in postnatal retinal vessels and internal organs including the gastrointestinal (GI) tract in mice...
November 29, 2016: Nature Communications
https://www.readbyqxmd.com/read/27895795/growth-differentiating-factor-15-gdf-15-a-potential-biomarker-and-therapeutic-target-for-cancer-associated-weight-loss
#11
Lorena Lerner, Jeno Gyuris, Richard Nicoletti, James Gifford, Brian Krieger, Aminah Jatoi
Growth differentiating factor-15 (GDF-15), also known as macrophage inhibiting factor-1, is a member of the transforming growth factor-β superfamily, which has been implicated in cancer-associated weight loss. The present study investigated the association between cancer-associated weight loss and plasma GDF-15 concentration, as well as other biomarkers, in patients with metastatic lung or exocrine pancreatic cancer. A total of 218 patients were enrolled over a 1-year period. The patient cohort included 152 patients with incurable lung cancer and 66 patients with incurable pancreatic cancer...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27885276/immunoregulation-by-members-of-the-tgf%C3%AE-superfamily
#12
WanJun Chen, Peter Ten Dijke
The transforming growth factor-β (TGFβ) superfamily is encoded by 33 genes and includes TGFβ, bone morphogenetic proteins (BMPs) and activins. Although TGFβ is well recognized as a crucial regulator of immune responses, the immunoregulatory functions of other TGFβ family members are less clear. However, recent evidence suggests that BMPs and activins have important roles in regulating immune responses. In this Review, we briefly outline the signalling pathways of the TGFβ superfamily and discuss new insights into the immunoregulatory functions of BMPs and activins in the context of infection, inflammation and cancer...
November 25, 2016: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/27883945/recent-advances-in-the-treatment-of-lower-risk-non-del-5q-myelodysplastic-syndromes-mds
#13
REVIEW
Antonio Almeida, Pierre Fenaux, Alan F List, Azra Raza, Uwe Platzbecker, Valeria Santini
Patients with lower-risk myelodysplastic syndromes (MDS) are affected primarily by symptoms of chronic anemia and fatigue rather than progression to acute myeloid leukemia. Severe thrombocytopenia, although less common in lower-risk MDS, is associated with increased risk of bleeding. For anemic patients, the principal aim of treatment is to improve anemia and decrease red blood cell transfusions. For transfusion-dependent patients with lower-risk MDS without chromosome 5q deletion [non-del(5q) MDS], there are limited effective treatments...
November 13, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27883118/cachexia
#14
A I Graul, M Stringer, L Sorbera
Cachexia is a multiorgan, multifactorial and often irreversible wasting syndrome associated with cancer and other serious, chronic illnesses including AIDS, chronic heart failure, chronic kidney disease and chronic obstructive pulmonary disease. Treatment of the patient with cachexia is currently targeted to correcting the two underlying features of the condition: anorexia and metabolic disturbances. Greater understanding of the mechanisms behind cachexia and muscle wasting have led to new therapeutic possibilities, however...
September 2016: Drugs of Today
https://www.readbyqxmd.com/read/27881824/two-tissue-resident-progenitor-lineages-drive-distinct-phenotypes-of-heterotopic-ossification
#15
Devaveena Dey, Jana Bagarova, Sarah J Hatsell, Kelli A Armstrong, Lily Huang, Joerg Ermann, Ashley J Vonner, Yue Shen, Agustin H Mohedas, Arthur Lee, Elisabeth M W Eekhoff, Annelies van Schie, Marie B Demay, Charles Keller, Amy J Wagers, Aris N Economides, Paul B Yu
Fibrodysplasia ossificans progressiva (FOP), a congenital heterotopic ossification (HO) syndrome caused by gain-of-function mutations of bone morphogenetic protein (BMP) type I receptor ACVR1, manifests with progressive ossification of skeletal muscles, tendons, ligaments, and joints. In this disease, HO can occur in discrete flares, often triggered by injury or inflammation, or may progress incrementally without identified triggers. Mice harboring an Acvr1(R206H) knock-in allele recapitulate the phenotypic spectrum of FOP, including injury-responsive intramuscular HO and spontaneous articular, tendon, and ligament ossification...
November 23, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27881396/involvement-of-infiltrating-macrophage-derived-activin-a-in-the-progression-of-renal-damage-in-mrl-lpr-mice
#16
Anastasie Thilela Kadiombo, Akito Maeshima, Ken Kayakabe, Hidekazu Ikeuchi, Toru Sakairi, Yoriaki Kaneko, Keiju Hiromura, Yoshihisa Nojima
Lupus nephritis is a life-threatening complication of systemic lupus erythematosus (SLE). Various growth factors, cytokines, and chemokines are implicated in the development of SLE. However, the pathophysiological processes involved in the development of lupus nephritis still remain unclear. In this study, we examined the involvement of activin A, a member of TGF-β superfamily, in the progression of renal damage in lupus-prone MRL-lpr mice. Activin A was was not expressed in the kidneys of normal C57BL/6 mice but was detectable in perivascular infiltrating CD68-positive cells in the kidneys of MRL-lpr mice...
November 23, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27874028/a-mouse-model-of-hereditary-hemorrhagic-telangiectasia-generated-by-transmammary-delivered-immunoblocking-of-bmp9-and-bmp10
#17
Santiago Ruiz, Haitian Zhao, Pallavi Chandakkar, Prodyot K Chatterjee, Julien Papoin, Lionel Blanc, Christine N Metz, Fabien Campagne, Philippe Marambaud
Hereditary hemorrhagic telangiectasia (HHT) is a potentially life-threatening genetic vascular disorder caused by loss-of-function mutations in the genes encoding activin receptor-like kinase 1 (ALK1), endoglin, Smad4, and bone morphogenetic protein 9 (BMP9). Injections of mouse neonates with BMP9/10 blocking antibodies lead to HHT-like vascular defects in the postnatal retinal angiogenesis model. Mothers and their newborns share the same immunity through the transfer of maternal antibodies during lactation...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27870893/activin-receptor-type-iib-inhibition-improves-muscle-phenotype-and-function-in-a-mouse-model-of-spinal-muscular-atrophy
#18
Min Liu, David W Hammers, Elisabeth R Barton, H Lee Sweeney
Spinal muscular atrophy (SMA) is a devastating neurodegenerative disorder that causes progressive muscle atrophy and weakness. Using adeno-associated virus-mediated gene transfer, we evaluated the potential to improve skeletal muscle weakness via systemic, postnatal inhibition of either myostatin or all signaling via the activin receptor type IIB (ActRIIB). After demonstrating elevated p-SMAD3 content and differential content of ActRIIB ligands, 4-week-old male C/C SMA model mice were treated intraperitoneally with 1x1012 genome copies of pseudotype 2/8 virus encoding a soluble form of the ActRIIB extracellular domain (sActRIIB) or protease-resistant myostatin propeptide (dnMstn) driven by a liver specific promoter...
2016: PloS One
https://www.readbyqxmd.com/read/27869117/genome-wide-rnai-screen-reveals-alk1-mediates-ldl-uptake-and-transcytosis-in-endothelial-cells
#19
Jan R Kraehling, John H Chidlow, Chitra Rajagopal, Michael G Sugiyama, Joseph W Fowler, Monica Y Lee, Xinbo Zhang, Cristina M Ramírez, Eon Joo Park, Bo Tao, Keyang Chen, Leena Kuruvilla, Bruno Larriveé, Ewa Folta-Stogniew, Roxana Ola, Noemi Rotllan, Wenping Zhou, Michael W Nagle, Joachim Herz, Kevin Jon Williams, Anne Eichmann, Warren L Lee, Carlos Fernández-Hernando, William C Sessa
In humans and animals lacking functional LDL receptor (LDLR), LDL from plasma still readily traverses the endothelium. To identify the pathways of LDL uptake, a genome-wide RNAi screen was performed in endothelial cells and cross-referenced with GWAS-data sets. Here we show that the activin-like kinase 1 (ALK1) mediates LDL uptake into endothelial cells. ALK1 binds LDL with lower affinity than LDLR and saturates only at hypercholesterolemic concentrations. ALK1 mediates uptake of LDL into endothelial cells via an unusual endocytic pathway that diverts the ligand from lysosomal degradation and promotes LDL transcytosis...
November 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27865758/bone-morphogenetic-protein-2-and-transforming-growth-factor-%C3%AE-1-inhibit-the-expression-of-the-proinflammatory-cytokine-il-34-in-rheumatoid-arthritis-synovial-fibroblasts
#20
Marguerite Chemel, Regis Brion, Aude-Isabelle Segaliny, Audrey Lamora, Celine Charrier, Benedicte Brulin, Yves Maugars, Benoit Le Goff, Dominique Heymann, Franck Verrecchia
IL-34 is a proinflammatory cytokine implicated in rheumatoid arthritis (RA). The current study aimed to assess the IL-34 expression in response to two members of the transforming growth factor (TGF)-β family, TGF-β1 and bone morphogenetic protein (BMP)-2, in synovial fibroblasts from RA patients. IL-34, TGF-β1, and BMP-2 productions were measured in patient synovial fluids by enzyme-linked immunosorbent assay. IL-34 mRNA levels were quantified by real-time quantitative PCR in human synovial fibroblasts and murine mesenchymal stem cells...
November 17, 2016: American Journal of Pathology
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