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Amphiregulin

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https://www.readbyqxmd.com/read/29682205/ferric-citrate-and-ferric-edta-but-not-ferrous-sulfate-drive-amphiregulin-mediated-activation-of-the-map-kinase-erk-in-gut-epithelial-cancer-cells
#1
Nathalie M Scheers, Dora I A Pereira, Nuno Faria, Jonathan J Powell
Ferric chelates may be used as oral iron supplements or phosphate binders but both ferric citrate and ferric EDTA have been shown to promote tumor burden in murine models of colon cancer. Here we studied their effects on cancer cell growth, at typical supplemental iron levels encountered in the gastrointestinal tract (0.01-0.2 mM). Caco-2 and/or Hutu-80 cells were exposed to these forms of chelated iron or to ferrous sulfate and outcomes were assessed using cell proliferation assays, proteome profiler arrays, western blot, and ELISA...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29670537/impact-of-different-tidal-volume-levels-at-low-mechanical-power-on-ventilator-induced-lung-injury-in-rats
#2
Lillian Moraes, Pedro L Silva, Alessandra Thompson, Cintia L Santos, Raquel S Santos, Marcos V S Fernandes, Marcelo M Morales, Vanessa Martins, Vera L Capelozzi, Marcelo G de Abreu, Paolo Pelosi, Patricia R M Rocco
Tidal volume (VT ) has been considered the main determinant of ventilator-induced lung injury (VILI). Recently, experimental studies have suggested that mechanical power transferred from the ventilator to the lungs is the promoter of VILI. We hypothesized that, as long as mechanical power is kept below a safe threshold, high VT should not be injurious. The present study aimed to investigate the impact of different VT levels and respiratory rates (RR) on lung function, diffuse alveolar damage (DAD), alveolar ultrastructure, and expression of genes related to inflammation [interleukin (IL)-6], alveolar stretch (amphiregulin), epithelial [club cell secretory protein (CC)16] and endothelial [intercellular adhesion molecule (ICAM)-1] cell injury, and extracellular matrix damage [syndecan-1, decorin, and metalloproteinase (MMP)-9] in experimental acute respiratory distress syndrome (ARDS) under low-power mechanical ventilation...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29662625/adam17-inhibition-enhances-platinum-efficiency-in-ovarian-cancer
#3
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/29645082/soluble-st2-sst2-regulation-by-rhinovirus-rv-and-25-oh-vitamin-d3-in-the-blood-of-asthmatic-children
#4
Patricia Haag, Himanshu Sharma, Manfred Rauh, Theodor Zimmermann, Tytti Vuorinen, Nikolaos G Papadopoulos, Scott T Weiss, Susetta Finotto
Paediatric asthma exacerbations are often caused by Rhinovirus (RV). Moreover, 25(OH)-Vitamin D3 (=25(OH) VitD3) deficiency during infancy was found associated with asthma. Here, we investigated the innate immune responses to RV and their possible modulation by 25(OH) VitD3 serum levels in a preschool cohort of children with and without asthma. The innate lymphoid cell type 2 (ILC2)-associated marker, ST2 was found upregulated in the blood cells of asthmatic children with low serum levels of 25(OH)VitD3 in the absence of RV in their airways...
April 12, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29623414/ilc2s-in-infectious-diseases-and-organ-specific-fibrosis
#5
REVIEW
Markus Kindermann, Lisa Knipfer, Imke Atreya, Stefan Wirtz
Type 2 immune responses evolved to provide host protection against parasitic infections and to support the repair of infection-induced tissue injury. However, persistent chronic organ damage can result in dysregulated production of critical type 2 cytokines supporting tissue remodeling and fibrosis development. Recently, group 2 innate lymphoid cells (ILC2s) were newly described as central innate mediators of type 2 responses. In particular, by secretion of the cytokines IL-5, IL-9, and IL-13 and the growth factor amphiregulin in response to the release of tissue-derived alarmins, ILC2s have been shown to substantially contribute to both the dismissal of metazoan parasites and the repair of infection-dependent or sterile tissue damage...
March 26, 2018: Seminars in Immunopathology
https://www.readbyqxmd.com/read/29574638/long-chain-omega-3-polyunsaturated-fatty-acids-modulate-mammary-gland-composition-and-inflammation
#6
Saraswoti Khadge, Geoffrey M Thiele, John Graham Sharp, Timothy R McGuire, Lynell W Klassen, Paul N Black, Concetta C DiRusso, James E Talmadge
Studies in rodents have shown that dietary modifications as mammary glands (MG) develop, regulates susceptibility to mammary tumor initiation. However, the effects of dietary PUFA composition on MGs in adult life, remains poorly understood. This study investigated morphological alterations and inflammatory microenvironments in the MGs of adult mice fed isocaloric and isolipidic liquid diets with varying compositions of omega (ω)-6 and long-chain (Lc)-ω3FA that were pair-fed. Despite similar consumption levels of the diets, mice fed the ω-3 diet had significantly lower body-weight gains, and abdominal-fat and mammary fat pad (MFP) weights...
March 25, 2018: Journal of Mammary Gland Biology and Neoplasia
https://www.readbyqxmd.com/read/29550478/cullin-3-regulates-adams-mediated-ectodomain-shedding-of-amphiregulin
#7
Hironao Nakayama, Tomohisa Sakaue, Masashi Maekawa, Ayako Fujisaki, Shigeki Higashiyama
A disintegrin and metalloproteinase (ADAM) family are crucial enzymes for ectodomain shedding of multiple substrates and are involved in diverse biologic and pathologic processes. However, the molecular mechanism underlying substrate selectivity of ADAMs is poorly understood. In this study, we observed that disruption of actin polymerization by pharmacological inhibitors, latrunculin A (LatA) and cytochalasin D (CyD), induced ectodomain shedding of epidermal growth factor (EGF) family ligands. Induced shedding activity by LatA or CyD was suppressed by a metalloprotease inhibitor KB-R7785, indicating that ADAMs-mediated shedding is tightly controlled by actin cytoskeleton...
April 30, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29540993/the-egfr-adam17-axis-in-chronic-obstructive-pulmonary-disease-and-cystic-fibrosis-lung-pathology
#8
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/29527422/cellular-prion-protein-and-%C3%AE-synuclein-overexpression-in-ls-174t-colorectal-cancer-cell-drives-endothelial-proliferation-to-differentiation-switch
#9
Sing-Hui Ong, Kai-Wey Goh, Cornelius Kwang-Lee Chieng, Yee-How Say
Background: Tumor-induced angiogenesis is an imperative event in pledging new vasculature for tumor metastasis. Since overexpression of neuronal proteins gamma-synuclein (γ-Syn) and cellular prion protein (PrPC ) is always detected in advanced stages of cancer diseases which involve metastasis, this study aimed to investigate whether γ-Syn or PrPC overexpression in colorectal adenocarcinoma, LS 174T cells affects angiogenesis of endothelial cells, EA.hy 926 (EA). Methods: EA cells were treated with conditioned media (CM) of LS 174T-γ-Syn or LS 174T-PrP, and their proliferation, invasion, migration, adhesion and ability to form angiogenic tubes were assessed using a range of biological assays...
2018: PeerJ
https://www.readbyqxmd.com/read/29503399/effect-of-pre-in-vitro-maturation-with-camp-modulators-on-the-acquisition-of-oocyte-developmental-competence-in-cattle
#10
Satoshi Sugimura, Tadayuki Yamanouchi, Maria Grazia Palmerini, Yutaka Hashiyada, Kei Imai, Robert B Gilchrist
The administration of follicle-stimulating hormone (FSH) prior to oocyte retrieval improves oocyte developmental competence. During bovine embryo production in vitro, however, oocytes are typically derived from FSH-unprimed animals. In the current study, we examined the effect of pre-in vitro maturation (IVM) with cAMP modulators, also known as the second messengers of FSH, on the developmental competence of oocytes derived from small antral follicles (2-4 mm) of FSH-unprimed animals. Pre-IVM with N6,2'-O-dibutyryladenosine 3',5'-cyclicmonophosphate (dbcAMP) and 3-isobutyl-1-methylxanthine (IBMX) for 2 h improved the blastocyst formation in oocytes stimulated by FSH or amphiregulin (AREG)...
March 2, 2018: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/29489470/biologic-impact-of-mechanical-power-at-high-and-low-tidal-volumes-in-experimental-mild-acute-respiratory-distress-syndrome
#11
Raquel S Santos, Ligia de A Maia, Milena V Oliveira, Cíntia L Santos, Lillian Moraes, Eliete F Pinto, Cynthia Dos S Samary, Joana A Machado, Anna Carolinna Carvalho, Marcos Vinícius de S Fernandes, Vanessa Martins, Vera L Capelozzi, Marcelo M Morales, Thea Koch, Marcelo Gama de Abreu, Paolo Pelosi, Pedro L Silva, Patricia R M Rocco
BACKGROUND: The authors hypothesized that low tidal volume (VT) would minimize ventilator-induced lung injury regardless of the degree of mechanical power. The authors investigated the impact of power, obtained by different combinations of VT and respiratory rate (RR), on ventilator-induced lung injury in experimental mild acute respiratory distress syndrome (ARDS). METHODS: Forty Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 h, 32 rats were randomly assigned to be mechanically ventilated (2 h) with a combination of different VT (6 ml/kg and 11 ml/kg) and RR that resulted in low and high power...
February 28, 2018: Anesthesiology
https://www.readbyqxmd.com/read/29485489/biological-response-to-time-controlled-adaptive-ventilation-depends-on-acute-respiratory-distress-syndrome-etiology
#12
Pedro Leme Silva, Fernanda Ferreira Cruz, Cynthia Dos Santos Samary, Lillian Moraes, Raquel Ferreira de Magalhães, Marcos Vinicius de S Fernandes, Rebeca Bose, Vitor B Pelegati, Hernandes F Carvalho, Vera Luiza Capelozzi, Joshua Satalin, Louis Gatto, Penny Andrews, Nader Habashi, Gary Nieman, Patricia R M Rocco
OBJECTIVES: To compare a time-controlled adaptive ventilation strategy, set in airway pressure release ventilation mode, versus a protective mechanical ventilation strategy in pulmonary and extrapulmonary acute respiratory distress syndrome with similar mechanical impairment. DESIGN: Animal study. SETTING: Laboratory investigation. SUBJECTS: Forty-two Wistar rats. INTERVENTIONS: Pulmonary acute respiratory distress syndrome and extrapulmonary acute respiratory distress syndrome were induced by instillation of Escherichia coli lipopolysaccharide intratracheally or intraperitoneally, respectively...
February 26, 2018: Critical Care Medicine
https://www.readbyqxmd.com/read/29483579/hypoxia-inducible-factor-2-alpha-dependent-induction-of-amphiregulin-dampens-myocardial-ischemia-reperfusion-injury
#13
Michael Koeppen, Jae W Lee, Seong-Wook Seo, Kelley S Brodsky, Simone Kreth, Ivana V Yang, Peter M Buttrick, Tobias Eckle, Holger K Eltzschig
Myocardial ischemia-reperfusion injury (IRI) leads to the stabilization of the transcription factors hypoxia-inducible factor 1-alpha (HIF1-alpha) and hypoxia-inducible factor 2-alpha (HIF2-alpha). While previous studies implicate HIF1-alpha in cardioprotection, the role of HIF2-alpha remains elusive. Here we show that HIF2-alpha induces the epithelial growth factor amphiregulin (AREG) to elicit cardioprotection in myocardial IRI. Comparing mice with inducible deletion of Hif1a or Hif2a in cardiac myocytes, we show that loss of Hif2-alpha increases infarct sizes...
February 26, 2018: Nature Communications
https://www.readbyqxmd.com/read/29421153/nuclear-translocation-of-igf1r-by-intracellular-amphiregulin-contributes-to-the-resistance-of-lung-tumour-cells-to-egfr-tki
#14
Marie Guerard, Thomas Robin, Pascal Perron, Anne-Sophie Hatat, Laurence David-Boudet, Laetitia Vanwonterghem, Benoit Busser, Jean-Luc Coll, Sylvie Lantuejoul, Beatrice Eymin, Amandine Hurbin, Sylvie Gazzeri
Many Receptor Tyrosine Kinases translocate from the cell surface to the nucleus in normal and pathological conditions, including cancer. Here we report the nuclear expression of insulin-like growth factor-1 receptor (IGF1R) in primary human lung tumours. Using lung cancer cell lines and lung tumour xenografts, we demonstrate that the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) gefitinib induces the nuclear accumulation of IGF1R in mucinous lung adenocarcinoma by a mechanism involving the intracellular re-localization of the growth factor amphiregulin...
April 28, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29420611/inductions-of-granulosa-cell-luteinization-and-cumulus-expansion-are-dependent-on-the-fibronectin-integrin-pathway-during-ovulation-process-in-mice
#15
Hiroya Kitasaka, Tomoko Kawai, S A Masudul Hoque, Takashi Umehara, Youko Fujita, Masayuki Shimada
It has been known that EGF-like factor secreted from LH-stimulated granuloma cells acts on granulosa cells and cumulus cells to induce ovulation process. Granulosa cells are changed the morphology with differentiating cell functions to produce progesterone. Cumulus cells are detached to make a space between the cells to accumulate hyaluronan rich matrix. LH also changes extracellular matrix (ECM) components including fibronectin in the follicular walls and granulosa cell layers. EGF like factor and fibronectin synergistically play important roles in numerous cell functions, especially cancer cell migration, estimating that fibronectin would impact on granulosa cells and cumulus cells...
2018: PloS One
https://www.readbyqxmd.com/read/29419396/expanding-primary-cells-from-mucoepidermoid-and-other-salivary-gland-neoplasms-for-genetic-and-chemosensitivity-testing
#16
Ahmad M Alamri, Xuefeng Liu, Jan K Blancato, Bassem R Haddad, Weisheng Wang, Xiaogang Zhong, Sujata Choudhary, Ewa Krawczyk, Bhaskar V Kallakury, Bruce J Davidson, Priscilla A Furth
Restricted availability of cell and animal models is a rate-limiting step for investigation of salivary gland neoplasm pathophysiology and therapeutic response. Conditionally reprogrammed cell (CRC) technology enables establishment of primary epithelial cell cultures from patient material. This study tested a translational workflow for acquisition, expansion and testing of CRC-derived primary cultures of salivary gland neoplasms from patients presenting to an academic surgical practice. Results showed that cultured cells were sufficient for epithelial cell-specific transcriptome characterization to detect candidate therapeutic pathways and fusion genes, and for screening for cancer risk-associated single nucleotide polymorphisms (SNPs) and driver gene mutations through exome sequencing...
January 29, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29351448/extracellular-oxidation-in-cystic-fibrosis-airway-epithelium-causes-enhanced-egfr-adam17-activity
#17
Marta Stolarczyk, Guido Veit, Andrea Schnúr, Mieke Veltman, Gergely L Lukacs, Bob J Scholte
The EGF receptor (EGFR)/a disintegrin and metalloproteinase 17 (ADAM17) signaling pathway mediates the shedding of growth factors and secretion of cytokines and is involved in chronic inflammation and tissue remodeling. Since these are hallmarks of cystic fibrosis (CF) lung disease, we hypothesized that CF transmembrane conductance regulator (CFTR) deficiency enhances EGFR/ADAM17 activity in human bronchial epithelial cells. In CF bronchial epithelial CFBE41o- cells lacking functional CFTR (iCFTR- ) cultured at air-liquid interface (ALI) we found enhanced ADAM17-mediated shedding of the EGFR ligand amphiregulin (AREG) compared with genetically identical cells with induced CFTR expression (iCFTR+ )...
April 1, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29349588/amphiregulin-enhances-cardiac-fibrosis-and-aggravates-cardiac-dysfunction-in-mice-with-experimental-myocardial-infarction-partly-through-activating-egfr-dependent-pathway
#18
Liang Liu, Xian Jin, Cui-Fen Hu, Ya-Ping Zhang, Zhong'e Zhou, Rong Li, Cheng-Xing Shen
Cardiac fibrosis (CF), a main process of ventricular remodeling after myocardial infarction (MI), plays a crucial role in the pathogenesis of heart failure (HF) post-MI. It is known that amphiregulin (AR) is involved in fibrosis of several organs. However, the expression of AR and its role post-MI are yet to be determined. This study aimed to investigate the impact of AR on CF post-MI and related mechanisms. Significantly upregulated AR expression was evidenced in the infarct border zone of MI mice in vivo and the AR secretion was enhanced in macrophages, but not in cardiac fibroblasts...
January 18, 2018: Basic Research in Cardiology
https://www.readbyqxmd.com/read/29341420/transgenic-mice-specifically-expressing-amphiregulin-in-white-adipose-tissue-showed-less-adipose-tissue-mass
#19
Bo Yang, Takahiro Kumoto, Takeshi Arima, Minako Nakamura, Yohei Sanada, Thanutchaporn Kumrungsee, Yusuke Sotomaru, Masayuki Shimada, Noriyuki Yanaka
To determine adipocytokines that play a regulatory role during obesity development, we explored the genes that encode growth factors and investigated the physiological functions for adipose tissue development. Here, we isolated amphiregulin (Areg) gene whose expression was significantly up-regulated in obese adipose tissues. Areg mRNA level was positively correlated with macrophage marker gene expression in adipose tissues in vivo. Unexpectedly, Areg transgenic mice showed less adipose tissue mass with increased mRNA expression levels of Tnf-α and peroxisome proliferator-activated receptor γ coactivator 1α (Pgc-1α) and delayed white adipose tissue development during the convalescent stage in a dextran sodium sulfate-induced colitis model...
January 17, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/29319804/effects-of-agricultural-organic-dusts-on-human-lung-resident-mesenchymal-stem-stromal-cell-function
#20
Tara M Nordgren, Kristina L Bailey, Art J Heires, Dawn Katafiasz, Debra J Romberger
Agricultural organic dust exposures trigger harmful airway inflammation, and workers experiencing repetitive dust exposures are at increased risk for lung disease. Mesenchymal stem/stromal cells (MSCs) regulate wound repair processes in the lung, and may contribute to either proresolution or -fibrotic lung responses. It is unknown how organic dust exposures alter lung-resident MSC activation and proinflammatory versus prorepair programs in the lung. To address this gap in knowledge, we isolated human lung-resident MSC from lung tissue...
April 1, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
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