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https://www.readbyqxmd.com/read/28903487/from-the-cover-arsenic-induces-hippocampal-neuronal-apoptosis-and-cognitive-impairments-via-an-up-regulated-bmp2-smad-dependent-reduced-bdnf-trkb-signaling-in-rats
#1
Rukmani Pandey, Vipin Rai, Juhi Mishra, Kapil Mandrah, Somendu Kumar Roy, Sanghamitra Bandyopadhyay
Arsenic promotes hippocampal neuronal damage inducing cognitive impairments. However, mechanism arbitrating arsenic-mediated cognitive deficits remains less-known. Here, we identified that chronic exposure to environmentally relevant doses of arsenic increased apoptosis, characterized by caspase-3 activation, poly(ADP-ribose) polymerase cleavage and Terminal deoxynucleotidyl transferase dUTP nick-end labeling of rat hippocampal neurons, marked by NeuN. Investigating apoptotic mechanism through invivo and invitro studies revealed that arsenic promoted bone morphogenetic protein-2 (BMP2) expression, supported by increased BMP-receptor2 (BMPR2) and p-Smad1/5 in hippocampal neurons...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28893916/the-role-of-activins-in-hepcidin-regulation-during-malaria
#2
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/28881850/transforming-growth-factor-%C3%AE-a-potential-biomarker-and-therapeutic-target-of-ventricular-remodeling
#3
REVIEW
Yuan Ma, Hai Zou, Xing-Xing Zhu, Jie Pang, Qiang Xu, Qin-Yang Jin, Ya-Hui Ding, Bing Zhou, Dong-Sheng Huang
Transforming growth factor β (TGF-β) is a multifunctional cytokine that is synthesized by many types of cells and regulates the cell cycle. Increasing evidence has led to TGF-β receiving increased and deserved attention in recent years because it may play a potentially novel and critical role in the development and progression of myocardial fibrosis and the subsequent progress of ventricular remodeling (VR). Numerous studies have highlighted a crucial role of TGF-β in VR and suggest potential therapeutic targets of the TGF-β signaling pathways for VR...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881580/selective-compounds-enhance-osteoblastic-activity-by-targeting-hect-domain-of-ubiquitin-ligase-smurf1
#4
Yuan Zhang, Cheng Wang, Yu Cao, Yongqing Gu, Lingqiang Zhang
The HECT-type ubiquitin ligase Smurf1 (Smad ubiquitination regulatory factor-1) plays the prominent role in regulation of bone formation, embryonic development, and tumorigenesis by directing the ubiquitin-proteasomal degradation of specific targets. In contrast with RING-type E3s, the catalytic HECT domain of Smurf1 firstly binds to and then transfers ubiquitin (Ub) molecules onto the substrates. The Smurf1-Ub interaction is required for Smurf1 catalytic ligase activity to promote substrate degradation. However, so far specific regulators or compounds controlling Smurf1-Ub interaction and the ligase activity have not been identified...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28880957/mapping-the-stk4-hippo-signaling-network-in-prostate-cancer-cell
#5
Damien Ready, Kader Yagiz, Pooneh Amin, Yuksel Yildiz, Vincent Funari, Serdar Bozdag, Bekir Cinar
Dysregulation of MST1/STK4, a key kinase component of the Hippo-YAP pathway, is linked to the etiology of many cancers with poor prognosis. However, how STK4 restricts the emergence of aggressive cancer remains elusive. Here, we investigated the effects of STK4, primarily localized in the cytoplasm, lipid raft, and nucleus, on cell growth and gene expression in aggressive prostate cancer. We demonstrated that lipid raft and nuclear STK4 had superior suppressive effects on cell growth in vitro and in vivo compared with cytoplasmic STK4...
2017: PloS One
https://www.readbyqxmd.com/read/28869862/bmp-2-and-bmp-9-binding-specificities-with-alk-3-in-aqueous-solution-with-dynamics
#6
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
https://www.readbyqxmd.com/read/28864813/the-immunophilin-fkbp12-inhibits-hepcidin-expression-by-binding-the-bmp-type-i-receptor-alk2-in-hepatocytes
#7
Silvia Colucci, Alessia Pagani, Mariateresa Pettinato, Irene Artuso, Antonella Nai, Clara Camaschella, Laura Silvestri
The expression of the key regulator of iron homeostasis hepcidin is activated by the BMP-SMAD pathway in response to iron and inflammation and among drugs, by rapamycin, which inhibits mTOR in complex with the immunophilin FKBP12. FKBP12 interacts with BMP type I receptors to avoid uncontrolled signaling. By pharmacologic and genetic studies we identify FKBP12 as a novel hepcidin regulator. Sequestration of FKBP12 by rapamycin or tacrolimus activates hepcidin both in vitro and in murine hepatocytes. Acute tacrolimus treatment transiently increases hepcidin in wild type mice...
September 1, 2017: Blood
https://www.readbyqxmd.com/read/28857319/transcription-factors-intricate-players-of-the-bone-morphogenetic-protein-signaling-pathway
#8
REVIEW
M Ampuja, A Kallioniemi
Bone morphogenetic proteins (BMPs) are a family of growth factors, some of which are known by the name growth and differentiation factor (GDF). BMPs were discovered in the 1960s in an attempt to find factors capable of inducing bone formation. By the end of 1980s, several different BMPs had been found and to date, around 20 members are known. Together with TGFβ, nodal and activins, they comprise the TGFβ superfamily. BMPs are known to regulate cell fate both in development and adult tissues, and as such they are also involved in many disease states...
August 31, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28855331/drosophila-nociceptive-sensitization-requires-bmp-signaling-via-the-canonical-smad-pathway
#9
Taylor L Follansbee, Kayla J Gjelsvik, Courtney L Brann, Aidan L McParland, Colin A Longhurst, Michael J Galko, Geoffrey K Ganter
Nociceptive sensitization is a common feature in chronic pain, but its basic cellular mechanisms are only partially understood. The present study used the Drosophila melanogaster model system and a candidate gene approach to identify novel components required for modulation of an injury-induced nociceptive sensitization pathway presumably downstream of Hedgehog. This study demonstrates that RNAi silencing of a member of the Bone Morphogenetic Protein (BMP) signaling pathway, Decapentaplegic (Dpp), specifically in the Class IV multidendritic nociceptive neuron, significantly attenuated ultraviolet injury-induced sensitization...
August 30, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28842696/adhesion-to-stromal-cells-mediates-imatinib-resistance-in-chronic-myeloid-leukemia-through-erk-and-bmp-signaling-pathways
#10
Atul Kumar, Jina Bhattacharyya, Bithiah Grace Jaganathan
Chronic myeloid leukemia (CML) is characterized by abnormal proliferation of myeloid cells which when untreated leads to bone marrow failure. Imatinib mesylate (IM) is the first line of therapy for treatment of CML and results in remission in most cases. However, a significant percentage of patients develop chemoresistance to IM, which might be due to the presence of chemoresistant cells in the bone marrow. In the current study, we explored the role of cell-cell interaction of CML cells with the bone marrow stromal cells in the development of chemoresistance in CML...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28838258/the-protective-effects-of-bone-morphogenetic-protein-7-against-epithelial-injury-and-matrix-metalloproteases-upregulation-induced-by-silica-in-vitro
#11
D Liang, G An, Z Zhu, Y Wang, G Yang, X Li, P Niu, L Chen, L Tian
OBJECTIVE: We investigate the effects of bone morphogenetic protein-7 (BMP-7) on models with silica-induced and macrophage-mediated fibrosis and its possible mechanisms in vitro. METHODS: Rat alveolar II epithelial (RLE-6TN) cells were incubated with the supernatant of mouse macrophage-like cells (RAW264.7) and treated with 0, 25, 50, and 100 μg/mL silica. Using Western blotting, the epithelial markers (surfactant proteins-C and E-cadherin) and the mesenchymal markers (fibronectin (FN) and viminten (Vim)) were detected...
September 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28831209/different-modulatory-effects-of-il-17-il-22-and-il-23-on-osteoblast-differentiation
#12
Jing-Ru Zhang, Dan-Dan Pang, Qiang Tong, Xia Liu, Ding-Feng Su, Sheng-Ming Dai
OBJECTIVES: To examine the expressions of IL-17, IL-22, and IL-23 receptors in four osteoblast models and the effects of IL-17, IL-22, and IL-23 on osteoblasts. METHODS: Gene expression levels of receptors, alkaline phosphatase (ALP), osteocalcin (OCN), and Runt-related transcription factor 2 (Runx-2), were evaluated by RT-PCR and real-time RT-PCR. Proliferative responses and cell cycle analysis were detected by a CCK-8 assay and flow cytometry, respectively. ALP activity and ALP mass were detected by an ALP activity assay and ALP staining, respectively...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28821740/irs4-a-novel-modulator-of-bmp-smad-and-akt-signalling-during-early-muscle-differentiation
#13
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
#14
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/28815688/bmp2-controls-iron-homeostasis-in-mice-independent-of-bmp6
#15
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/28814721/acceleration-of-osteoblast-differentiation-by-a-novel-osteogenic-compound-dmp-pyt-through-activation-of-both-the-bmp-and-wnt-pathways
#16
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
#17
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/28805484/disparate-phospho-smad2-levels-in-advanced-type-2-diabetes-patients-with-diabetic-nephropathy-and-early-experimental-db-db-mouse-model
#18
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/28765970/bmp-7-enhances-snon-mrna-expression-in-renal-tubular-epithelial-cells-under-high-glucose-conditions
#19
Yuanyuan Wang, Ying Xiao, Shuang Li, Lei Shi, Lirong Liu, Yingying Zhang, Mingjun Shi, Bing Guo
The present study aimed to identify any association between bone morphogenetic protein‑7 (BMP‑7) and the expression of the transcriptional co‑repressor Ski‑related novel protein N (SnoN), in addition to alterations in tubulointerstitial fibrosis, during the development and progression of diabetic nephropathy (DN). Streptozotocin was injected into the tail veins of 20 healthy and specific pathogen‑free male Sprague‑Dawley rats. The rats were sacrificed to detect the appropriate biochemical indicators of renal pathological alterations following 24 weeks...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28760815/endothelial-cells-respond-to-the-direction-of-mechanical-stimuli-through-smad-signaling-to-regulate-coronary-artery-size
#20
Aruna Poduri, Brian Raftrey, Andrew H Chang, Siyeon Rhee, Mike Van, Kristy Red-Horse
How mechanotransduction intersects with chemical and transcriptional factors to shape organogenesis is an important question in developmental biology. This is particularly relevant to the cardiovascular system, which uses mechanical signals from flowing blood to stimulate cytoskeletal and transcriptional responses that form a highly efficient vascular network. Using this system, artery size and structure are tightly regulated, but the underlying mechanisms are poorly understood. Here, we demonstrate that deletion of Smad4 increased the diameter of coronary arteries during embryonic development, a phenotype that followed the initiation of blood flow...
July 31, 2017: Development
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