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ADAM17

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https://www.readbyqxmd.com/read/29776906/blood-induced-bone-loss-in-murine-hemophilic-arthropathy-is-prevented-by-blocking-the-irhom2-adam17-tnf%C3%AE-pathway
#1
Coline Haxaire, Narine Hakobyan, Tania Pannellini, Camila Carballo, David McIlwain, Tak W Mak, Scott Rodeo, Suchitra Acharya, Daniel Li, Jackie Szymonifka, Xiangqian Song, Sébastien Monette, Alok Srivastava, Jane E Salmon, Carl P Blobel
Hemophilic arthropathy (HA) is a debilitating degenerative joint disease that is a major manifestation of the bleeding disorder Hemophilia A. HA typically begins with hemophilic synovitis (HS) that resembles inflammatory arthritides such as rheumatoid arthritis (RA) and frequently results in bone loss in patients. A major cause of RA is inappropriate release of the pro-inflammatory cytokine tumor necrosis factor α (TNFα) by the TNFα convertase (TACE, also referred to as ADAM17) and its regulator, iRhom2...
May 18, 2018: Blood
https://www.readbyqxmd.com/read/29776401/adam-17-is-a-poor-prognostic-indicator-for-patients-with-hilar-cholangiocarcinoma-and-is-regulated-by-foxm1
#2
Xiaodong Jiao, Wenlong Yu, Jianxin Qian, Ying Chen, Peilian Wei, Wenzheng Fang, Guanzhen Yu
BACKGROUND: A-disintegrin and metalloproteinases (ADAMs) are members of a family of multidomain transmembrane and secreted proteins. Specific ADAMs are upregulated in human cancers and correlated with tumor progression and poor outcome, but rarely studied in human hilar cholangiocarcinoma (HC). This study aimed to explore the expression profiles of ADAMs and their potential underlying mechanisms promoting cancer progression. METHODS: mRNA expression of ADAM-9, - 10, - 11, - 12, - 15, - 17, - 28, and - 33 was analyzed in human hilar cholangiocarcinoma (HC) samples...
May 18, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29766392/excessive-glutamate-stimulation-impairs-ace2-activity-through-adam17-mediated-shedding-in-cultured-cortical-neurons
#3
Jiaxi Xu, Srinivas Sriramula, Eric Lazartigues
The excitotoxicity of glutamate plays an important role in the progression of various neurological disorders via participating in inflammation and neuronal damage. In this study, we identified the role of excessive glutamate stimulation in the modulation of angiotensin-converting enzyme type 2 (ACE2), a critical component in the compensatory axis of the renin-angiotensin system (RAS). In primary cultured cortical neurons, high concentration of glutamate (100 µM) significantly reduced the enzymatic activity of ACE2...
May 15, 2018: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/29751002/adam17-deficient-mice-model-the-transcriptional-signature-of-human-atopic-dermatitis
#4
Therese Woodring, Tetsuro Kobayashi, Doyoung Kim, Keisuke Nagao
No abstract text is available yet for this article.
May 8, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29700308/foxm1-drives-adam17-egfr-activation-loop-to-promote-mesenchymal-transition-in-glioblastoma
#5
Chunli Zhang, Xiu Han, Xiao Xu, Zhengrong Zhou, Xi Chen, Yu Tang, Jie Cheng, Nida Fatima Moazzam, Fei Liu, Jing Xu, Wanxin Peng, Fengyi Du, Bin Zhang, Zhiwen Song, Jian Zeng, Aihua Gong
Mesenchymal transition (MES transition) is a hallmark of glioblastoma multiforme (GBM), however, the mechanism regulating the process remains to be elucidated. Here we report that FoxM1 drives ADAM17/EGFR activation loop to promote MES transition in GBM. Firstly, FoxM1 expression was positively associated with ADAM17 expression, and their expression was correlated with the mesenchymal features and overall patient survival of GBM. Overexpressing FoxM1 or ADAM17 increased the mesenchymal phenotype of glioma cells, which could be reversed by silencing FoxM1 or ADAM17...
April 27, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29662625/adam17-inhibition-enhances-platinum-efficiency-in-ovarian-cancer
#6
Nina Hedemann, Christoph Rogmans, Susanne Sebens, Daniela Wesch, Manuel Reichert, Dirk Schmidt-Arras, Hans-Heinrich Oberg, Ulrich Pecks, Marion van Mackelenbergh, Jörg Weimer, Norbert Arnold, Nicolai Maass, Dirk O Bauerschlag
Chemotherapeutic resistance evolves in about 70 % of ovarian cancer patients and is a major cause of death in this tumor entity. Novel approaches to overcome these therapeutic limitations are therefore highly warranted. A disintegrin and metalloprotease 17 (ADAM17) is highly expressed in ovarian cancer and required for releasing epidermal growth factor receptor (EGFR) ligands like amphiregulin (AREG). This factor has recently been detected in ascites of advanced stage ovarian cancer patients. However, it is not well understood, whether and how ADAM17 might contribute to chemo resistance of ovarian cancer...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29618514/activation-of-stimulator-of-interferon-genes-sting-induces-adam17-mediated-shedding-of-the-immune-semaphorin-sema4d
#7
Kou Motani, Hidetaka Kosako
Stimulator of interferon genes (STING) is an endoplasmic reticulum (ER)-resident membrane protein that mediates cytosolic pathogen DNA-induced innate immunity and inflammatory responses in host defenses. STING is activated by cyclic di-nucleotides and is then translocated to the Golgi apparatus, an event that triggers STING assembly with the downstream enzyme TANK-binding kinase 1 (TBK1). This assembly leads to the phosphorylation of the transcription factor interferon regulatory factor 3 (IRF3), which, in turn, induces expression of type-I interferon (IFN) and chemokine genes...
April 4, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29617412/tissue-inhibitor-of-metalloproteinase-3-timp-3-induces-fas-dependent-apoptosis-in-human-vascular-smooth-muscle-cells
#8
William R English, Heather Ireland-Zecchini, Andrew H Baker, Trevor D Littlewood, Martin R Bennett, Gillian Murphy
Over expression of Tissue Inhibitor of Metalloproteinases-3 (TIMP-3) in vascular smooth muscle cells (VSMCs) induces apoptosis and reduces neointima formation occurring after saphenous vein interposition grafting or coronary stenting. In studies to address the mechanism of TIMP-3-driven apoptosis in human VSMCs we find that TIMP-3 increased activation of caspase-8 and apoptosis was inhibited by expression of Cytokine response modifier A (CrmA) and dominant negative FAS-Associated protein with Death Domain (FADD)...
2018: PloS One
https://www.readbyqxmd.com/read/29561187/increased-urinary-angiotensin-converting-enzyme-2-ace2-and-neprilysin-nep-in-type-2-diabetic-patients
#9
Sridevi Gutta, Nadja Grobe, Meenasri Kumbaji, Hassan Osman, Mohammad Saklayen, Gengxin Li, Khalid M Elased
ACE2 and NEP are metalloproteases which are highly expressed in the renal proximal tubules. ACE2 and NEP generate renoprotective angiotensin (1-7) from angiotensin II (Ang II) and Ang I, respectively, and therefore could have a major role in chronic kidney disease (CKD). Recent data demonstrated increased urinary ACE2 in diabetic patients with CKD and kidney transplants. We tested the hypothesis that urinary ACE2, NEP and ADAM17 are increased and could be risk predictors of CKD in diabetic patients. Urinary and plasma ACE2, NEP, and ADAM17 were investigated in twenty healthy nondiabetics (ND), and forty diabetic patients with normoalbuminuria (Dnormo), microalbuminuria (Dmicro) and macroalbuminuria (Dmacro) using ELISA, Western blot, fluorogenic and novel mass spectrometric-based enzyme assays...
March 21, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29560732/human-umbilical-cord-blood-serum-derived-%C3%AE-secretase-functional-testing-in-alzheimer-s-disease-mouse-models
#10
Ahsan Habib, Huayan Hou, Takashi Mori, Jun Tian, Jin Zeng, Shengnuo Fan, Brian Giunta, Paul R Sanberg, Darrell Sawmiller, Jun Tan
Alzheimer's disease (AD) is an age-related disorder that affects cognition. Our previous studies showed that the neuroprotective fragment of amyloid procurer protein (APP) metabolite, soluble APPα (sAPPα), interferes with β-site APP-cleaving enzyme 1 (BACE1, β-secretase) cleavage and reduces amyloid-β (Aβ) generation. In an attempt to identify approaches to restore sAPPα levels, we found that human cord blood serum (CBS) significantly promotes sAPPα production compared with adult blood serum (ABS) and aged blood serum (AgBS) in Chinese hamster ovary cells stably expressing wild-type human APP...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29560122/the-enhanced-susceptibility-of-adam-17-hypomorphic-mice-to-dss-induced-colitis-is-not-ameliorated-by-loss-of-ripk3-revealing-an-unexpected-function-of-adam-17-in-necroptosis
#11
Johaiber Fuchslocher Chico, Maren Falk-Paulsen, Anne Luzius, Carina Saggau, Barbara Ruder, Julia Bolik, Dirk Schmidt-Arras, Andreas Linkermann, Christoph Becker, Philip Rosenstiel, Stefan Rose-John, Dieter Adam
The disintegrin metalloprotease ADAM17 has a critical role in intestinal inflammation and regeneration in mice, as illustrated by the dramatically increased susceptibility of ADAM17 hypomorphic (ADAM17ex/ex ) mice to dextran sulfate sodium (DSS)-induced colitis. Similarly, necroptosis has been implicated in inflammatory responses in the intestine. In this study, we have investigated the contribution of necroptosis to ADAM17-regulated intestinal inflammation in vivo by crossing ADAM17ex/ex mice with mice that lack the necroptotic core protein RIPK3...
February 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29540993/the-egfr-adam17-axis-in-chronic-obstructive-pulmonary-disease-and-cystic-fibrosis-lung-pathology
#12
REVIEW
Marta Stolarczyk, Bob J Scholte
Chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) share molecular mechanisms that cause the pathological symptoms they have in common. Here, we review evidence suggesting that hyperactivity of the EGFR/ADAM17 axis plays a role in the development of chronic lung disease in both CF and COPD. The ubiquitous transmembrane protease A disintegrin and metalloprotease 17 (ADAM17) forms a functional unit with the EGF receptor (EGFR), in a feedback loop interaction labeled the ADAM17/EGFR axis. In airway epithelial cells, ADAM17 sheds multiple soluble signaling proteins by proteolysis, including EGFR ligands such as amphiregulin (AREG), and proinflammatory mediators such as the interleukin 6 coreceptor (IL-6R)...
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29510400/adam17-mediated-ectodomain-shedding-of-toll-like-receptor-4-as-a-negative-feedback-regulation-in-lipopolysaccharide-activated-aortic-endothelial-cells
#13
Won Seok Yang, Jin Ju Kim, Mee Jeong Lee, Eun Kyoung Lee, Su-Kil Park
BACKGROUND/AIMS: Lipopolysaccharide (LPS)-activated monocytes/macrophages develop endotoxin tolerance in part by reducing cell surface toll-like receptor 4 (TLR4) through cluster of differentiation 14 (CD14)-dependent endocytosis. In case of endothelial cells, CD14 is expressed in low copy numbers as compared with monocytes/macrophages. Thus, we explored how endothelial cells regulate TLR4 expression after LPS stimulation. METHODS: Cultured human aortic endothelial cells (HAECs) were treated with LPS...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29499360/ursolic-acid-prevents-angiotensin-ii-induced-abdominal-aortic-aneurysm-in-apolipoprotein-e-knockout-mice
#14
Maocai Zhai, Junyi Guo, Haiyan Ma, Wei Shi, David Jou, Dan Yan, Tianshu Liu, Jingwen Tao, Jialin Duan, Yina Wang, Sheng Li, Jiagao Lv, Chenglong Li, Jiayuh Lin, Cuntai Zhang, Li Lin
BACKGROUND AND AIMS: Abdominal aortic aneurysms (AAA) is a chronic inflammatory disease in which signal transducer and activator of transcription 3 (STAT3), and disintegrin and metalloproteinase 17 (ADAM17) play important roles. However, it remains unclear whether ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, can have an impact on STAT3 and ADAM17 and hence influence the formation of AAA. The objective of this study was to characterize the potential effect of UA on the pathogenesis of AAA and on STAT3 and ADAM17...
April 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29495171/-effect-of-paraquat-on-the-expression-of-a-disintegrin-and-metalloproteinase-17-in-a549-cells
#15
W Y Fang, C W Lin, B F Wang, S G Feng
Objective: Construct a paraquat (PQ) cell fibrosis model in vitro, observe the effect of PQ on the expression of a disintegrin and metalloproteinase-17 (ADAM17) in A549 cells, and explore the role of ADAM17 in the pulmonary fibrosis induced by PQ poisoning. Methods: A549 cells are divided into normal control group, different concentration of PQ groups, CCK-8 is used to detect cell viability, screening concentration and time of PQ, cell morphology is observed under microscope; Enzyme-linked immunosorbent assay (ELISA) detectes fibrosis markers of collagen type I (Col I) and fibronectin (FN) expression...
January 20, 2018: Chinese Journal of Industrial Hygiene and Occupational Diseases
https://www.readbyqxmd.com/read/29475600/metalloprotease-adam17-regulates-porcine-epidemic-diarrhea-virus-infection-by-modifying-aminopeptidase-n
#16
Jian Zhang, Longjun Guo, Lijun Yang, Jiayu Xu, Lu Zhang, Li Feng, Hongyan Chen, Yue Wang
Porcine epidemic diarrhea virus (PEDV) is a causative agent of porcine epidemic diarrhea (PED). PED, characterized by acute diarrhea, vomiting, dehydration, has caused serious economic losses in pig industry worldwide. Here, we demonstrate that activation of a disintergrin and metalloprotease 17 (ADAM17) induced the decrease of PEDV infection in HEK293 and IPEC-J2 cells and the downregulation of cell surface aminopeptidase N (APN) expression, an important entry factor for PEDV infection. Furthermore, overexpression of ADAM17 suppressed PEDV infection in HEK293 and IPEC-J2 cells, whereas ablation of ADAM17 expression using ADAM17 specific siRNA resulted in a corresponding increase of PEDV infection and an upregulation of cell surface APN expression...
April 2018: Virology
https://www.readbyqxmd.com/read/29472497/adam17-is-required-for-egf-r-induced-intestinal-tumors-via-il-6-trans-signaling
#17
Stefanie Schmidt, Neele Schumacher, Jeanette Schwarz, Simone Tangermann, Lukas Kenner, Michaela Schlederer, Maria Sibilia, Markus Linder, Annelore Altendorf-Hofmann, Thomas Knösel, Elisabeth S Gruber, Georg Oberhuber, Julia Bolik, Ateequr Rehman, Anupam Sinha, Juliane Lokau, Philipp Arnold, Anne-Sophie Cabron, Friederike Zunke, Christoph Becker-Pauly, Adele Preaudet, Paul Nguyen, Jennifer Huynh, Shoukat Afshar-Sterle, Ashwini L Chand, Jürgen Westermann, Peter J Dempsey, Christoph Garbers, Dirk Schmidt-Arras, Philip Rosenstiel, Tracy Putoczki, Matthias Ernst, Stefan Rose-John
Colorectal cancer is treated with antibodies blocking epidermal growth factor receptor (EGF-R), but therapeutic success is limited. EGF-R is stimulated by soluble ligands, which are derived from transmembrane precursors by ADAM17-mediated proteolytic cleavage. In mouse intestinal cancer models in the absence of ADAM17, tumorigenesis was almost completely inhibited, and the few remaining tumors were of low-grade dysplasia. RNA sequencing analysis demonstrated down-regulation of STAT3 and Wnt pathway components...
April 2, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29464088/deciphering-microrna-targets-in-pancreatic-cancer-using-mircomb-r-package
#18
Maria Vila-Casadesús, Elena Vila-Navarro, Giulia Raimondi, Cristina Fillat, Antoni Castells, Juan José Lozano, Meritxell Gironella
MiRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression. They play important roles in cancer but little is known about the specific functions that each miRNA exerts in each type of cancer. More knowledge about their specific targets is needed to better understand the complexity of molecular networks taking part in cancer. In this study we report the miRNA-mRNA interactome occurring in pancreatic cancer by using a bioinformatic approach called miRComb, which combines tissue expression data with miRNA-target prediction databases (TargetScan, miRSVR and miRDB)...
January 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29434796/adam-proteases-involved-in-inflammation-are-differentially-altered-in-patients-with-gastritis-or-ulcer
#19
Nuray Erin, Sema Türker, Özlem Elpek, Bülent Yildirim
ADAM metallopeptidase domain (ADAM)9, 10 and 17 have α-secretase activity that regulates ectodomain shedding of factors involved in inflammation, cell proliferation, angiogenesis, and wound healing. The secretase activity of ADAM proteins is known to induce an inflammatory response. However, under certain conditions, a lack of secretase activity may induce inflammation suggesting differential roles of ADAM proteins with secretase activity. To the best of our knowledge, the present study evaluated the changes in α-secretase activity and expression of associated ADAM proteases (ADAM9, 10 and 17) in the gastric mucosa of patients with gastritis and ulcers, for the first time...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29393483/short-hairpin-rna-mediated-gene-silencing-of-adam17-inhibits-the-growth-of-breast-cancer-mcf%C3%A2-7-cells-in-vitro-and-in-vivo-and-its-mechanism-of-action
#20
Baoshan Hu, Xiangchao Meng, Yan Zhang, Mohammad Monir Hossain, Lijun Wu, Yuanyuan Zhang, Xiaobing Peng, Xuepeng Zhang
A disintegrin and metalloprotease 17 (ADAM17) is highly expressed in many malignant tumors and is closely related to their development. We showed in a previous study that silencing of ADAM17 by siRNA inhibited the growth of MCF‑7 breast cancer cells in vitro and in vivo. In the present study, we investigated the effects of ADAM17-short hairpin RNA (ADAM17‑shRNA) on MCF‑7 breast cancer cells and explored the potential action pathway. In vitro, transfection of shRNAs was performed using a lentivirus, and the effects of ADAM17‑shRNA on invasion, proliferation and cell cycle distribution of MCF‑7 cells were assessed by Boyden chamber method, real‑time cell analysis and flow cytometry, respectively...
April 2018: Oncology Reports
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