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BMP AND smad

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https://www.readbyqxmd.com/read/29130990/increased-bone-morphogenetic-protein-signaling-in-the-cutaneous-vasculature-of-patients-with-calciphylaxis
#1
Sagar U Nigwekar, Pawina Jiramongkolchai, Florian Wunderer, Emily Bloch, Rika Ichinose, Rosalynn M Nazarian, Ravi I Thadhani, Rajeev Malhotra, Donald B Bloch
BACKGROUND: The objective of this study was to investigate the role of bone morphogenetic protein (BMP) signal transduction in the pathogenesis of calciphylaxis. METHODS: Skin biopsy specimens were obtained from 18 patients with, and 12 patients without, calciphylaxis. Tissue sections were stained with antibodies directed against BMP effector proteins phosphorylated-SMAD (p-SMAD) 1/5/9, inhibitor of DNA 1 (Id1), inhibitor of DNA 3 (Id3), and Runx2. The intensity of staining was scored semi-quantitatively as strong versus weak or absent...
November 9, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/29129677/upregulated-bmp6-pathway-involved-in-the-pathogenesis-of-a%C3%AE-toxicity-in-vivo
#2
Sun Lin, Li Wei, Yang Ping, Li Xia, Xiao Shifu
In our previous work, we demonstrated the protective effect of BMP6 on neuron against Aβ toxicity in vitro. In the present study, our aim was to determine the effects of BMP6 in Aβ toxicity in vivo. Firstly, we evaluated the levels and localization of endogenous BMP6 in APP/PS1 transgenic mice. Secondly, dose-response effects of exogenous BMP6 and BMP6 pathway antagonists were tested in transgenic CL2006C. elegans (expressing Aβ3-42) lifespan and locomotor activity. We have three findings: 1) BMP6 was upregulated in the hippocampus in APP/PS1 mice...
November 9, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29115380/combination-treatment-of-adipose-derived-stem-cells-and-adiponectin-attenuates-pulmonary-arterial-hypertension-in-rats-by-inhibiting-pulmonary-arterial-smooth-muscle-cell-proliferation-and-regulating-the-ampk-bmp-smad-pathway
#3
Li Luo, Wuhong Zheng, Guili Lian, Huaning Chen, Ling Li, Changsheng Xu, Liangdi Xie
The present study aimed to assess the effects of therapy with adiponectin (APN) gene-modified adipose-derived stem cells (ADSCs) on pulmonary arterial hypertension (PAH) in rats and the underlying cellular and molecular mechanisms. ADSCs were successfully isolated from the rats and characterized. ADSCs were effectively infected with the green fluorescent protein (GFP)-empty (ADSCs-V) or the APN-GFP (ADSCs-APN) lentivirus and the APN expression was evaluated by ELISA. Sprague-Dawley rats were administered monocrotaline (MCT) to develop PAH...
October 31, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29113418/role-of-growth-differentiation-factor-11-in-development-physiology-and-disease
#4
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/29107070/inflammation-driven-colon-neoplasmatogenesis-in-upa-deficient-mice-is-associated-with-an-increased-expression-of-runx-transcriptional-regulators
#5
Hara Afaloniati, George S Karagiannis, Alexandros Hardas, Theofilos Poutahidis, Katerina Angelopoulou
Deregulation of the bone morphogenetic protein (BMP) pathway has been documented in colorectal cancer (CRC). Previously, we investigated possible associations between urokinase-type plasminogen activator (uPA) deficiency and expression of extracellular constituents of BMP signaling in a newly developed mouse model of inflammation-driven intestinal neoplasmatogenesis, in which chronic colitis and CRC are induced using dextran sodium sulfate (DSS). In this report, we explored the contribution of intracellular components of Smad-mediated BMP signal transduction using the same model...
October 26, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29103804/fibrinogen-activates-bmp-signaling-in-oligodendrocyte-progenitor-cells-and-inhibits-remyelination-after-vascular-damage
#6
Mark A Petersen, Jae Kyu Ryu, Kae-Jiun Chang, Ainhoa Etxeberria, Sophia Bardehle, Andrew S Mendiola, Wanjiru Kamau-Devers, Stephen P J Fancy, Andrea Thor, Eric A Bushong, Bernat Baeza-Raja, Catriona A Syme, Michael D Wu, Pamela E Rios Coronado, Anke Meyer-Franke, Stephanie Yahn, Lauriane Pous, Jae K Lee, Christian Schachtrup, Hans Lassmann, Eric J Huang, May H Han, Martina Absinta, Daniel S Reich, Mark H Ellisman, David H Rowitch, Jonah R Chan, Katerina Akassoglou
Blood-brain barrier (BBB) disruption alters the composition of the brain microenvironment by allowing blood proteins into the CNS. However, whether blood-derived molecules serve as extrinsic inhibitors of remyelination is unknown. Here we show that the coagulation factor fibrinogen activates the bone morphogenetic protein (BMP) signaling pathway in oligodendrocyte progenitor cells (OPCs) and suppresses remyelination. Fibrinogen induces phosphorylation of Smad 1/5/8 and inhibits OPC differentiation into myelinating oligodendrocytes (OLs) while promoting an astrocytic fate in vitro...
October 19, 2017: Neuron
https://www.readbyqxmd.com/read/29044189/tgf-%C3%AE-signalling-and-peg10-are-mutually-exclusive-and-inhibitory-in-chondrosarcoma-cells
#7
Naohiro Shinohara, Shingo Maeda, Yuhei Yahiro, Daisuke Sakuma, Kanehiro Matsuyama, Katsuyuki Imamura, Ichiro Kawamura, Takao Setoguchi, Yasuhiro Ishidou, Satoshi Nagano, Setsuro Komiya
Histological distinction between enchondroma and chondrosarcoma is difficult because of a lack of definitive biomarkers. Here, we found highly active transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) signalling in human chondrosarcomas compared with enchondromas by immunohistochemistry of phosphorylated SMAD3 and SMAD1/5. In contrast, the chondrogenic master regulator SOX9 was dramatically down-regulated in grade 1 chondrosarcoma. Paternally expressed gene 10 (PEG10) was identified by microarray analysis as a gene overexpressed in chondrosarcoma SW1353 and Hs 819...
October 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29040444/re-establishment-of-energy-balance-in-a-male-mouse-model-with-pomc-neuron-deletion-of-bmpr1a
#8
Kristy L Townsend, Christopher Madden, Magdalena Blaszkiewicz, Lindsay McDougall, Domenico Tupone, Matthew D Lynes, Yuji Mishina, Paul Yu, Shaun Morrison, Yu-Hua Tseng
The regulation of energy balance involves complex processes in the brain, including coordination by hypothalamic neurons that contain pro-opiomelanocortin (POMC). We previously demonstrated that central bone morphogenetic protein 7 (BMP7) reduces appetite. Now we show that a type 1 BMP receptor, BMPR1A, is co-localized with POMC neurons and POMC-BMPR1A-KO mice are hyperphagic, revealing physiological involvement of BMP signaling in anorectic POMC neurons in the regulation of appetite. Surprisingly, the hyperphagic POMC-BMPR1A-KO mice exhibit a lack of obesity, even on a 45% high-fat diet...
October 9, 2017: Endocrinology
https://www.readbyqxmd.com/read/29027119/mollugin-enhances-the-osteogenic-action-of-bmp-2-via-the-p38-smad-signaling-pathway
#9
Seong-Hee Moon, Ikyon Kim, Seong Hwan Kim
Bone morphogenetic protein 2 (BMP-2) has been used clinically to encourage bone regeneration; although, there can be major side effects with larger doses. Therefore, there is a need to identify new small molecules to potentiate the osteogenic action of BMP-2. In this study, we investigated the effect of mollugin on bone formation in murine bi-potential mesenchymal progenitor C2C12 cells by combination with BMP-2. We found mollugin could enhance the BMP-2-mediated osteoblast differentiation of C2C12 cells. This was accompanied by the induction of other osteogenic BMPs...
October 12, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29021231/deletion-of-bmp6-worsens-the-phenotype-of-hjv-deficient-mice-and-attenuates-hepcidin-levels-reached-after-lps-challenge
#10
Chloé Latour, Céline Besson-Fournier, Ophélie Gourbeyre, Delphine Meynard, Marie-Paule Roth, Hélène Coppin
Lack of either BMP6 or the BMP co-receptor hemojuvelin (HJV) in mice leads to a similar phenotype with hepcidin insufficiency, hepatic iron loading, and extrahepatic iron accumulation in males. This is consistent with the current views that HJV is a co-receptor for BMP6 in hepatocytes. To determine whether BMP6 and HJV may also signal to hepcidin independently of each other, we intercrossed Hjv(-/-) and Bmp6(-/-) mice and compared the phenotype of animals of the F2 progeny. Loss of Bmp6 further repressed Smad signaling and hepcidin expression in the liver of Hjv(-/-) mice of both genders, and led to iron accumulation in the pancreas and the heart of females...
October 11, 2017: Blood
https://www.readbyqxmd.com/read/28981600/emodin-promotes-the-osteogenesis-of-mc3t3-e1-cells-via-bmp-9-smad-pathway-and-exerts-a-preventive-effect-in-ovariectomized-rats
#11
Xiaojing Chen, Shuang Zhang, Xiaoting Chen, Yan Hu, Jin Wu, Shuyan Chen, Jing Chang, Genfa Wang, Yanhong Gao
Emodin, a natural anthraquinone extracted from the Chinese herbs rhubarb and giant knotweed rhizome, has been reported to enhance osteoblast differentiation. However, the mechanisms underlying its ability to regulate osteogenesis are unclear. The objective of this study was to determine the role of emodin in osteoblast function in vitro and its osteoprotective effect in vivo. Emodin enhanced the differentiation and mineralization of MC3T3-E1 cells, as evidenced by elevated alkaline phosphatase activity and increased number of mineralized nodules...
October 1, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28976802/the-mixed-lineage-leukemia-4-mll4-methyltransferase-complex-is-involved-in-transforming-growth-factor-beta-tgf-%C3%AE-activated-gene-transcription
#12
Roy Baas, Hetty A A M van Teeffelen, Sjoerd J D Tjalsma, H Th Marc Timmers
Sma and Mad related (SMAD)-mediated Transforming Growth Factor β (TGF-β) and Bone Morphogenetic Protein (BMP) signaling is required for various cellular processes. The activated heterotrimeric SMAD protein complexes associate with nuclear proteins such as the histone acetyltransferases p300, PCAF and the Mixed Lineage Leukemia 4 (MLL4) subunit Pax Transactivation domain-Interacting Protein (PTIP) to regulate gene transcription. We investigated the functional role of PTIP and PTIP Interacting protein 1 (PA1) in relation to TGF-β-activated SMAD signaling...
October 4, 2017: Transcription
https://www.readbyqxmd.com/read/28971221/uncoupled-iron-homeostasis-in-type-2-diabetes-mellitus
#13
Sandro Altamura, Stefan Kopf, Julia Schmidt, Katja Müdder, Ana Rita da Silva, Peter Nawroth, Martina U Muckenthaler
Diabetes mellitus is frequently associated with iron overload conditions, such as primary and secondary hemochromatosis. Conversely, patients affected by type 2 diabetes mellitus (T2DM) show elevated ferritin levels, a biomarker for increased body iron stores. Despite these documented associations between dysregulated iron metabolism and T2DM, the underlying mechanisms are poorly understood. Here, we show that T2DM patients have reduced serum levels of hepcidin, the iron-regulated hormone that maintains systemic iron homeostasis...
October 3, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28928159/bmp4-induces-m2-macrophage-polarization-and-favors-tumor-progression-in-bladder-cancer
#14
Víctor G Martínez, Carolina Rubio, Mónica Martínez-Fernández, Cristina Segovia, Fernando López-Calderón, Marina Garín, Alicia Teijeira, Ester Munera-Maravilla, Alberto Varas, Rosa Sacedón, Felix Guerrero-Ramos, Felipe Villacampa, Federico de la Rosa, Daniel Castellano, Eduardo López-Collazo, Jesus M Paramio, Ángeles Vicente, Marta Dueñas
PURPOSE: Bladder cancer (BC) is a current clinical and social problem. At diagnosis, most patients present non-muscle invasive tumors, characterized by a high recurrence rate, which could progress to muscle invasive disease and metastasis. Bone morphogenetic protein (BMP)-dependent signaling arising from stromal bladder tissue mediates urothelial homeostasis by promoting urothelial cell differentiation. However, the possible role of BMP ligands in BC is still unclear. EXPERIMENTAL DESIGN: Tumor and normal tissue from 68 patients with urothelial cancer were prospectively collected and analyzed for expression of BMP and macrophage markers...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28923783/bmp7-induced-pten-inhibits-akt-and-prevents-renal-fibrosis
#15
Debra F Higgins, Leah M Ewart, Enda Masterson, Sadhbh Tennant, Gleb Grebnev, Marco Prunotto, Sylvia Pomposiello, Karin Conde-Knape, Finian M Martin, Catherine Godson
Bone morphogenetic protein-7 (BMP-7) counteracts pro-fibrotic effects of TGFβ1 in cultured renal cells and protects from fibrosis in acute and chronic renal injury models. Using the unilateral ureteral obstruction (UUO) model of chronic renal fibrosis, we investigated the effect of exogenous-rhBMP-7 on pro-fibrotic signaling pathways mediated by TGFβ1 and hypoxia. Mice undergoing UUO were treated with vehicle or rhBMP-7 (300μg/kg i.p.) every other day for eight days and kidneys analysed for markers of fibrosis and SMAD, MAPK, and PI3K signaling...
September 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28921936/sprouty2-is-involved-in-the-control-of-osteoblast-proliferation-and-differentiation-through-the-fgf-and-bmp-signaling-pathways
#16
Takaharu Taketomi, Tomohiro Onimura, Daigo Yoshiga, Daichi Muratsu, Terukazu Sanui, Takao Fukuda, Jingo Kusukawa, Seiji Nakamura
Fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) play essential roles in bone formation and osteoblast activity through the extracellular signal-regulated kinase 1/2 (ERK1/2) and Smad pathways. Sprouty family members are intracellular inhibitors of the FGF signaling pathway, and four orthologs of Sprouty have been identified in mammals. In vivo analyses have revealed that Sprouty2 is associated with bone formation. However, the mechanism by which the Sprouty family controls bone formation has not been clarified...
September 16, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28919027/macrolactin-f-inhibits-rankl-mediated-osteoclastogenesis-by-suppressing-akt-mapk-and-nfatc1-pathways-and-promotes-osteoblastogenesis-through-a-bmp-2-smad-akt-runx2-signaling-pathway
#17
Liang Li, Mahesh Sapkota, Ming Gao, Hyukjae Choi, Yunjo Soh
The balance between bone formation and bone resorption is maintained by osteoblasts and osteoclasts. In the current study, macrolactin F (MF) was investigated for novel biological activity on the receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis in primary bone marrow-derived macrophages (BMMs). We found that RANKL-induced osteoclast formation and differentiation from BMMs was significantly inhibited by MF in a dose-dependent manner without cytotoxicity. RANKL-induced F-actin ring formation and bone resorption activity in BMMs which was attenuated by MF...
November 15, 2017: European Journal of Pharmacology
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
#18
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
#19
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
#20
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
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