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BMP signalling

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https://www.readbyqxmd.com/read/28821740/irs4-a-novel-modulator-of-bmp-smad-and-akt-signalling-during-early-muscle-differentiation
#1
Gina Dörpholz, Arunima Murgai, Jerome Jatzlau, Daniel Horbelt, Mohammad Poorgholi Belverdi, Christina Heroven, Isabelle Schreiber, Gisela Wendel, Karen Ruschke, Sigmar Stricker, Petra Knaus
Elaborate regulatory networks of the Bone Morphogenetic Protein (BMP) pathways ensure precise signalling outcome during cell differentiation and tissue homeostasis. Here, we identified IRS4 as a novel regulator of BMP signal transduction and provide molecular insights how it integrates into the signalling pathway. We found that IRS4 interacts with the BMP receptor BMPRII and specifically targets Smad1 for proteasomal degradation consequently leading to repressed BMP/Smad signalling in C2C12 myoblasts while concomitantly activating the PI3K/Akt axis...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819210/zeb2-is-a-negative-regulator-of-midbrain-dopaminergic-axon-growth-and-target-innervation
#2
Shane V Hegarty, Sean L Wyatt, Laura Howard, Elke Stappers, Danny Huylebroeck, Aideen M Sullivan, Gerard W O'Keeffe
Neural connectivity requires neuronal differentiation, axon growth, and precise target innervation. Midbrain dopaminergic neurons project via the nigrostriatal pathway to the striatum to regulate voluntary movement. While the specification and differentiation of these neurons have been extensively studied, the molecular mechanisms that regulate midbrain dopaminergic axon growth and target innervation are less clear. Here we show that the transcription factor Zeb2 cell-autonomously represses Smad signalling to limit midbrain dopaminergic axon growth and target innervation...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819138/cooperative-interaction-of-bmp-signalling-and-foxn1-gene-dosage-determines-the-size-of-the-functionally-active-thymic-epithelial-compartment
#3
Jeremy B Swann, Brigitte Krauth, Christiane Happe, Thomas Boehm
Thymopoiesis strictly depends on the function of the Foxn1 transcription factor that is expressed in the thymic epithelium. During embryonic development, initial expression of the Foxn1 gene is induced in the pharyngeal endoderm by mesenchyme-derived BMP4 signals. Here, by engineering a time-delayed feedback system of BMP inhibition in mouse embryos, we demonstrate that thymopoiesis irreversibly fails if Foxn1 gene expression does not occur during a defining time span in mid-gestation. We also reveal an epistatic interaction between the extent of BMP signalling and the gene dosage of Foxn1...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28815688/bmp2-controls-iron-homeostasis-in-mice-independent-of-bmp6
#4
Susanna Canali, Chia-Yu Wang, Kimberly B Zumbrennen-Bullough, Abraham Bayer, Jodie L Babitt
Hepcidin is a key iron regulatory hormone that controls expression of the iron exporter ferroportin to increase the iron supply when needed to support erythropoiesis and other essential functions, but to prevent the toxicity of iron excess. The bone morphogenetic protein (BMP)-SMAD signaling pathway, through the ligand BMP6 and the co-receptor hemojuvelin, is a central regulator of hepcidin transcription in the liver in response to iron. Here, we show that dietary iron loading has a residual ability to induce Smad signaling and hepcidin expression in Bmp6-/- mice, effects that are blocked by a neutralizing BMP2/4 antibody...
August 17, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28815657/celecoxib-inhibits-osteoblast-differentiation-independent-of-cyclooxygenase-activity
#5
Atsushi Matsuyama, Sen Higashi, Saori Tanizaki, Takahiko Morotomi, Ayako Washio, Tomoko Ohsumi, Chiaki Kitamura, Hiroshi Takeuchi
Non-steroidal anti-inflammatory drugs (NSAIDs) exert their effects primarily by inhibiting the activity of cyclooxygenase (COX), thus suppressing prostaglandin synthesis. Some NSAIDs are known to perform functions other than pain control, such as suppressing tumour cell growth, independent of their COX-inhibiting activity. To identify NSAIDs with COX-independent activity, we examined various NSAIDs for their ability to inhibit osteoblastic differentiation using the mouse pre-osteoblast cell line MC3T3-E1. Only celecoxib and valdecoxib strongly inhibited osteoblastic differentiation, and this effect was not correlated with COX-inhibiting activity...
August 16, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28815565/generation-of-animal-form-by-the-chordin-tolloid-bmp-gradient-100%C3%A2-years-after-d-arcy-thompson
#6
Edward M De Robertis, Yuki Moriyama, Gabriele Colozza
The classic book "On Growth and Form" by naturalist D'Arcy Thompson was published 100 years ago. To celebrate this landmark, we present experiments in the Xenopus embryo that provide a framework for understanding how simple, quantitative transformations of a morphogen gradient might have affected evolution and morphological diversity of organisms. D'Arcy Thompson proposed that different morphologies might be generated by modifying physical parameters in an underlying system of Cartesian coordinates that pre-existed in Nature and arose during evolutionary history...
August 16, 2017: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/28814721/acceleration-of-osteoblast-differentiation-by-a-novel-osteogenic-compound-dmp-pyt-through-activation-of-both-the-bmp-and-wnt-pathways
#7
Su Jung Bae, Hye Joo Kim, Hee Yeon Won, Yong Ki Min, Eun Sook Hwang
Osteoblast differentiation is regulated through the successive activation of signaling molecules by a complex interplay of extracellular signals such as bone morphogenetic protein (BMP) and Wnt ligands. Numerous studies have identified natural as well as synthetic compounds with osteogenic activity through the regulation of either BMP/SMADs or the Wnt/β-catenin pathway. Here, we attempted to isolate small molecules that concurrently activated both SMADs and β-catenin, which led to the discovery of a novel potent osteogenic compound, DMP-PYT...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814648/zc4h2-stabilizes-smads-to-enhance-bmp-signalling-which-is-involved-in-neural-development-in-xenopus
#8
Pengcheng Ma, Biyu Ren, Xiangcai Yang, Bin Sun, Xiaoliang Liu, Qinghua Kong, Chaocui Li, Bingyu Mao
Bone morphogenetic proteins (BMPs) play vital roles in regulating stem cell maintenance, differentiation and embryonic development. Intracellularly, BMP signalling is mediated by Smad proteins, which are regulated post-transcriptionally through reversible phosphorylation and ubiquitination. ZC4H2 is a small nuclear protein associated with intellectual disability and neural development in humans. Here, we report that ZC4H2 is highly expressed in the developing neural system and is involved in neural patterning and BMP signalling in Xenopus Knockdown of ZC4H2 led to expansion of the expression of the pan neural plate marker Sox2 in Xenopus embryos...
August 2017: Open Biology
https://www.readbyqxmd.com/read/28811280/dan-nbl1-promotes-collective-neural-crest-migration-by-restraining-uncontrolled-invasion
#9
Rebecca McLennan, Caleb M Bailey, Linus J Schumacher, Jessica M Teddy, Jason A Morrison, Jennifer C Kasemeier-Kulesa, Lauren A Wolfe, Madeline M Gogol, Ruth E Baker, Philip K Maini, Paul M Kulesa
Neural crest cells are both highly migratory and significant to vertebrate organogenesis. However, the signals that regulate neural crest cell migration remain unclear. In this study, we test the function of differential screening-selected gene aberrant in neuroblastoma (DAN), a bone morphogenetic protein (BMP) antagonist we detected by analysis of the chick cranial mesoderm. Our analysis shows that, before neural crest cell exit from the hindbrain, DAN is expressed in the mesoderm, and then it becomes absent along cell migratory pathways...
August 15, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28808027/de-novo-mutations-in-inhibitors-of-wnt-bmp-and-ras-erk-signaling-pathways-in-non-syndromic-midline-craniosynostosis
#10
Andrew T Timberlake, Charuta G Furey, Jungmin Choi, Carol Nelson-Williams, Erin Loring, Amy Galm, Kristopher T Kahle, Derek M Steinbacher, Dawid Larysz, John A Persing, Richard P Lifton
Non-syndromic craniosynostosis (NSC) is a frequent congenital malformation in which one or more cranial sutures fuse prematurely. Mutations causing rare syndromic craniosynostoses in humans and engineered mouse models commonly increase signaling of the Wnt, bone morphogenetic protein (BMP), or Ras/ERK pathways, converging on shared nuclear targets that promote bone formation. In contrast, the genetics of NSC is largely unexplored. More than 95% of NSC is sporadic, suggesting a role for de novo mutations. Exome sequencing of 291 parent-offspring trios with midline NSC revealed 15 probands with heterozygous damaging de novo mutations in 12 negative regulators of Wnt, BMP, and Ras/ERK signaling (10...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28805484/disparate-phospho-smad2-levels-in-advanced-type-2-diabetes-patients-with-diabetic-nephropathy-and-early-experimental-db-db-mouse-model
#11
Lise Høj Thomsen, Morten Fog-Tonnesen, Lisbeth Nielsen Fink, Jenny Norlin, Amaya García de Vinuesa, Troels Krarup Hansen, Emile de Heer, Peter Ten Dijke, Alexander Rosendahl
Uncontrolled activation of transforming growth factor beta (TGF-β) family members is hypothesized to participate in type 2 diabetes (T2D) dependent diabetic nephropathy (DN). We evaluated and compared downstream activation of the Smad2-signaling pathway in kidney samples from T2D patients to kidneys from the T2D model of leptin receptor deficient db/db mouse. Furthermore, expression of TGF-β family members was evaluated to elucidate molecular mechanisms in the mouse model. Kidney samples from patients with advanced stages of DN showed elevated pSmad2 staining whereas db/db mouse kidneys surprisingly showed a decrease in pSmad2 in the tubular compartment...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28800317/identification-of-prostate-cancer-hub-genes-and-therapeutic-agents-using-bioinformatics-approach
#12
Enhao Fang, Xiuqing Zhang, Qi Wang, Daoming Wang
BACKGROUND: Prostate cancer (PCa) is the most common and the second leading cause of cancer-related death among men in America. As the molecular mechanism of PCa has not yet been completely discovered, identification of hub genes and potential drug of this disease is an important area of research that could provide new insights into exploring the mechanisms underlying PCa. OBJECTIVE: The aim of this study was to identify potential biomarkers and novel drug for prostate cancer treatment...
July 30, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28798778/tumorigenic-and-differentiation-potentials-of-embryonic-stem-cells-depend-on-tgf%C3%AE-family-signaling-lessons-from-teratocarcinoma-cells-stimulated-to-differentiate-with-retinoic-acid
#13
Olga Gordeeva, Sergey Khaydukov
A significant challenge for the development of safe pluripotent stem cell-based therapies is the incomplete in vitro differentiation of the pluripotent stem cells and the presence of residual undifferentiated cells initiating teratoma development after transplantation in recipients. To understand the mechanisms of incomplete differentiation, a comparative study of retinoic acid-induced differentiation of mouse embryonic stem (ES) and teratocarcinoma (EC) cells was conducted. The present study identified differences in proliferative activity, differentiation, and tumorigenic potentials between ES and EC cells...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28794168/notch-signaling-in-development-tissue-homeostasis-and-disease
#14
REVIEW
Chris Siebel, Urban Lendahl
Notch signaling is an evolutionarily highly conserved signaling mechanism, but in contrast to signaling pathways such as Wnt, Sonic Hedgehog, and BMP/TGF-β, Notch signaling occurs via cell-cell communication, where transmembrane ligands on one cell activate transmembrane receptors on a juxtaposed cell. Originally discovered through mutations in Drosophila more than 100 yr ago, and with the first Notch gene cloned more than 30 yr ago, we are still gaining new insights into the broad effects of Notch signaling in organisms across the metazoan spectrum and its requirement for normal development of most organs in the body...
October 1, 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28791357/synergistic-effects-of-fibroblast-growth-factor-2-and-bone-morphogenetic-protein-2-on-bone-induction
#15
Rongying Song, Dingding Wang, Rong Zeng, Ju Wang
The present study investigated the synergistic effect of co‑administering fibroblast growth factor‑2 (FGF‑2) and bone morphogenetic protein‑2 (BMP‑2) on osteoblastic differentiation in C2C12 cells and in rats. C2C12 murine myoblast cells represent a well‑accepted in vitro model system to study the ability of BMP‑2 to alter cell lineage from the myogenic to the osteogenic phenotype. The osteoblastic differentiation potency was determined by alkaline phosphatase (ALP) and Alizarin red S staining...
August 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28790933/mechanisms-of-smooth-muscle-cell-differentiation-are-distinctly-altered-in-thoracic-aortic-aneurysms-associated-with-bicuspid-or-tricuspid-aortic-valves
#16
Elena Ignatieva, Daria Kostina, Olga Irtyuga, Vladimir Uspensky, Alexey Golovkin, Natalia Gavriliuk, Olga Moiseeva, Anna Kostareva, Anna Malashicheva
Cellular and molecular mechanisms of thoracic aortic aneurysm are not clear and therapeutic approaches are mostly absent. Thoracic aortic aneurysm is associated with defective differentiation of smooth muscle cells (SMC) of aortic wall. Bicuspid aortic valve (BAV) comparing to tricuspid aortic valve (TAV) significantly predisposes to a risk of thoracic aortic aneurysms. It has been suggested recently that BAV-associated aortopathies represent a separate pathology comparing to TAV-associated dilations. The only proven candidate gene that has been associated with BAV remains NOTCH1...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28790014/bmp2-expression-in-the-endocardial-lineage-is-required-for-av-endocardial-cushion-maturation-and-remodeling
#17
Jacob G Saxon, Daniel R Baer, Julie A Barton, Travis Hawkins, Bingruo Wu, Thomas C Trusk, Stephen E Harris, Bin Zhou, Yuji Mishina, Yukiko Sugi
Distal outgrowth, maturation and remodeling of the endocardial cushion mesenchyme in the atrioventricular (AV) canal are the essential morphogenetic events during four-chambered heart formation. Mesenchymalized AV endocardial cushions give rise to the AV valves and the membranous ventricular septum (VS). Failure of these processes results in several human congenital heart defects. Despite this clinical relevance, the mechanisms governing how mesenchymalized AV endocardial cushions mature and remodel into the membranous VS and AV valves have only begun to be elucidated...
August 5, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28771228/uev1a-facilitates-osteosarcoma-differentiation-by-promoting-smurf1-mediated-smad1-ubiquitination-and-degradation
#18
Weiwei Zhang, Yuan Zhuang, Yiran Zhang, Xiaoran Yang, Hong Zhang, Guifen Wang, Wanqi Yin, Ruifeng Wang, Zhiling Zhang, Wei Xiao
Malignant bone tumor osteosarcoma (OS) displays high metastasis incidence and poor prognosis. Its stem cell properties could serve to explain tumor recurrence and resistance to conventional treatments. In this study, we identified UEV1A as a novel suppressor of OS. Elevated UEV1A diminishes stem cell properties of OS cells and drives them to terminal differentiation. Importantly, UEV1A-overexpressed OS cells delay proliferation and are more sensitive to chemotherapeutic agents than control cells. Uev1A appears to be involved in the BMP signaling pathway in which it collaborates with a ubiquitin E3 ligase Smurf1 to promote Smad1 degradation in a Ubc13-independent manner...
August 3, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28768899/aberrant-perichondrial-bmp-signaling-mediates-multiple-osteochondromagenesis-in-mice
#19
Toshihiro Inubushi, Satoshi Nozawa, Kazu Matsumoto, Fumitoshi Irie, Yu Yamaguchi
Multiple hereditary exostoses (MHE) is characterized by the development of numerous benign bony tumors (osteochondromas). Although it has been well established that MHE is caused by mutations in EXT1 and EXT2, which encode glycosyltransferase essential for heparan sulfate (HS) biosynthesis, the cellular origin and molecular mechanisms of MHE remain elusive. Here, we show that in Ext1 mutant mice, osteochondromas develop from mesenchymal stem cell-like progenitor cells residing in the perichondrium, and we show that enhanced BMP signaling in these cells is the primary signaling defect that leads to osteochondromagenesis...
August 3, 2017: JCI Insight
https://www.readbyqxmd.com/read/28768485/a-systematic-review-of-genetic-mutations-in-pulmonary-arterial-hypertension
#20
Gerardo Garcia-Rivas, Carlos Jerjes-Sánchez, David Rodriguez, José Garcia-Pelaez, Victor Trevino
BACKGROUND: Pulmonary arterial hypertension (PAH) is a group of vascular diseases that produce right ventricular dysfunction, heart failure syndrome, and death. Although the majority of patients appear idiopathic, accumulated research work combined with current sequencing technology show that many gene variants could be an important component of the disease. However, current guidelines, clinical practices, and available gene panels focus the diagnosis of PAH on a relatively low number of genes and variants associated with the bone morphogenic proteins and transforming Growth Factor-β pathways, such as the BMPR2, ACVRL1, CAV1, ENG, and SMAD9...
August 2, 2017: BMC Medical Genetics
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