DOCSLIB.ORG

Apparatus and Growth Hormone Receptor Signaling

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Apparatus and Growth Hormone Receptor Signaling Functional Interaction of Common γ-Chain and Growth Hormone Receptor Signaling Apparatus This information is current as Marsilio Adriani, Corrado Garbi, Giada Amodio, Ilaria of October 2, 2021. Russo, Marica Giovannini, Stefania Amorosi, Eliana Matrecano, Elena Cosentini, Fabio Candotti and Claudio Pignata J Immunol 2006; 177:6889-6895; ; doi: 10.4049/jimmunol.177.10.6889 http://www.jimmunol.org/content/177/10/6889 Downloaded from References This article cites 42 articles, 14 of which you can access for free at: http://www.jimmunol.org/content/177/10/6889.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on October 2, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2006 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Functional Interaction of Common ␥-Chain and Growth Hormone Receptor Signaling Apparatus1 Marsilio Adriani,* Corrado Garbi,† Giada Amodio,* Ilaria Russo,* Marica Giovannini,* Stefania Amorosi,* Eliana Matrecano,* Elena Cosentini,‡ Fabio Candotti,§ and Claudio Pignata2* We previously reported on an X-linked SCID (X-SCID) patient, who also had peripheral growth hormone (GH) hyporesponsive- ness and abnormalities of the protein phosphorylation events following GH receptor (GHR) stimulation. In the present study, we ␥ ␥ examined a potential role of common cytokine receptor -chain ( c) in GHR signaling using EBV-transformed lymphocytes from ␥ healthy subjects and c-negative X-SCID patients. We demonstrated that the proliferative response to GH stimulation of the B cell ␥ lines of c-negative patients was impaired despite a comparable cellular expression of GHR molecules to controls. In patients, after GH stimulation, no phosphorylation of STAT5 was observed. In addition, the molecule localization through confocal microscopy Downloaded from revealed that in B cell lines of patients no nuclear translocation of STAT5b following GH stimulation occurred differently from ␥ controls. Biochemical analysis of the nuclear extracts of c-negative cell lines provided further evidence that the amount of ␥ STAT5b and its phosphorylated form did not increase following GH stimulation. In patients, cells reconstituted with wild-type c abnormal biochemical and functional events were restored resulting in nuclear translocation of STAT5. Confocal experiments ␥ revealed that GHR and c were colocalized on the cell membrane. Our study demonstrates the existence of a previously unap- ␥ http://www.jimmunol.org/ preciated relationship between GHR-signaling pathway and c, which is required for the activation of STAT5b in B cell lines. These data also confirm that growth failure in X-SCID is primarily related to the genetic alteration of the IL2RG gene. The Journal of Immunology, 2006, 177: 6889–6895. evere combined immunodeficiencies represent a wide component of several receptors critical for the development and spectrum of illnesses, which differ in either the qualitative function of lymphocytes (3). To our knowledge, an extrahemopoi- or quantitative alterations of T, B, and NK cell (1). Most etic role of ␥ has not yet been demonstrated, although the abun- S c forms of SCID are associated with molecular alterations of genes dance of the protein in nonhemopoietic cells would imply addi- selectively expressed in hemopoietic cells and implicated in the tional functions for this element (4, 5). cell differentiation/activation process. Thus, classical symptoms We previously reported on a patient affected with X-SCID who by guest on October 2, 2021 are generally considered those related to the immunological im- received a bone marrow transplantation late at 5.2 years of age. In pairment that results in increased susceptibility to infections. Be- this patient, short stature became evident, and a peripheral growth cause patients usually die by the first year of age without an ef- hormone (GH) hyporesponsiveness associated with abnormalities fective treatment, the clinical phenotype is predominated by the of the protein phosphorylation events that occur following GH life-threatening problems. receptor (GHR) stimulation was demonstrated. X-linked SCID (X-SCID)3 is the most common form of the The GHR was the first identified member of the cytokine re- disease accounting for approximately half of all cases (2, 3). The ceptor class 1 superfamily, which includes receptors for erythro- gene responsible for X-SCID is IL2RG that encodes for the com- poietin, G-CSF, GM-CSF, IL-2–7, IL-9, IL-11, IL-12, and many ␥ ␥ mon cytokine receptor -chain ( c), a member of the cytokine other cytokines. Due to the lack of intrinsic kinase activity, mem- receptor class 1 superfamily. The molecule represents a shared bers of the cytokine receptor superfamily recruit and/or activate cytoplasmic tyrosine kinases to relay their cellular signal. The JAK2 represents the predominant nonreceptor tyrosine kinase re- *Department of Pediatrics, †Department of Cellular and Molecular Biology and Pa- quired for the initiation of GH signal transduction upon ligand ‡ thology, and Immunohematology Unit, “Federico II” University, Naples, Italy; and binding to the receptor (6, 7). However, GH also stimulates ty- §Genetics and Molecular Biology Branch, National Human Genome Research Insti- tute, National Institutes of Health, Bethesda, MD 20892 rosine phosphorylation of JAK1 (8, 9) and JAK3 (10) in certain Received for publication July 21, 2005. Accepted for publication August 16, 2006. cell lines. Signal transduction through GHR also involves a wide The costs of publication of this article were defrayed in part by the payment of page array of molecules, such as STATs 1, 3, and 5, ERK 1 and 2, and charges. This article must therefore be hereby marked advertisement in accordance PI3K-protein kinase B (7). Activation of STAT5b is considered a with 18 U.S.C. Section 1734 solely to indicate this fact. prominent event in GH signaling and is crucial for the regulation 1 This work was supported by Ministero della Salute-Roma and Regione Campania, of transcription of GH-responsive genes, including the gene en- Legge 502 and Ministero dell’Universita`e della Ricerca Scı`entifica e Tecnologica, Progetto di Rilevante Interesse Nazionale and by the Division of Intramural Research, coding for insulin-like growth factor (IGF)-I, which mediates National Human Genome Research Institute, National Institutes of Health. many of the GH biological functions (11–13). In our previous 2 Address correspondence and reprint request to Dr. Claudio Pignata, Department of study, mutational screening and expressional analysis failed to re- Pediatrics, Unit of Immunology, “Federico II” University, Via S. Pansini 5-80131, veal any molecular alteration of GHR, JAK2, and STAT5A/B genes in Naples, Italy. E-mail address: [email protected] the patient with X-SCID and peripheral GH hyporesponsiveness (14). 3 ␥ Abbreviations used in this paper: X-SCID, X-linked SCID; c, common cytokine ␥ receptor ␥-chain; GH, growth hormone; GHR, GH receptor; IGF, insulin-like growth Because we hypothesized a role for the c in GHR signaling, in factor; rGH, recombinant human GH; BCL, lymphoblastoid cell line; WT, wild type. this study, we evaluate the functional interaction between GHR Copyright © 2006 by The American Association of Immunologists, Inc. 0022-1767/06/$02.00 ␥ 6890 FUNCTIONAL INTERACTION BETWEEN c AND GHR and the common ␥ element in either freshly isolated or EBV-trans- Western blot formed lymphocytes from X-SCID patients and healthy subjects. Immunoblotting using phosphotyrosine mAb was performed as previously In particular, the functional response to GH stimulation, the pattern reported (14). Immunoblotting using specific Ab was performed according of GHR-induced protein tyrosine phosphorylation and GH-in- to the vendor protocols. In brief, protein samples separated by SDS-PAGE duced translocation from the cytoplasm to the nucleus of STAT5 were transferred onto Mixed Cellulose Esters membranes (Immobilon-NC ␮ were evaluated. We demonstrate the existence of a previously un- Mixed Cellulose Esters 0.45 m; Millipore). The membrane was incubated ␥ at room temperature for1hinblocking buffer consisting of 10% BSA in appreciated functional interaction between c and GHR. This in- wash buffer (10 mM Tris (pH 7.5), 100 mM NaCl, and 0.1% Tween 20). teraction leads to the activation and intranuclear translocation of The membrane was then washed three times in wash buffer and incubated the STAT5b protein. 1 h at room temperature or overnight at 4°C with the specific Ab. The membrane was then washed three times and an appropriate IgG HRP- conjugated secondary Ab was used for the second incubation. After further Materials and Methods washings, the membrane was developed with ECL-developing reagents, Reagents and exposed to x-ray films according to the manufacturer’s instructions (Amersham
Load more

Recommended publications
  • Receptor-Mediated Dimerization of JAK2 FERM Domains Is Required for JAK2 Activation Ryan D Ferrao, Heidi JA Wallweber, Patrick J Lupardus*
    RESEARCH ARTICLE Receptor-mediated dimerization of JAK2 FERM domains is required for JAK2 activation Ryan D Ferrao, Heidi JA Wallweber, Patrick J Lupardus* Department of Structural Biology, Genentech, Inc., South San Francisco, United States Abstract Cytokines and interferons initiate intracellular signaling via receptor dimerization and activation of Janus kinases (JAKs). How JAKs structurally respond to changes in receptor conformation induced by ligand binding is not known. Here, we present two crystal structures of the human JAK2 FERM and SH2 domains bound to Leptin receptor (LEPR) and Erythropoietin receptor (EPOR), which identify a novel dimeric conformation for JAK2. This 2:2 JAK2/receptor dimer, observed in both structures, identifies a previously uncharacterized receptor interaction essential to dimer formation that is mediated by a membrane-proximal peptide motif called the ‘switch’ region. Mutation of the receptor switch region disrupts STAT phosphorylation but does not affect JAK2 binding, indicating that receptor-mediated formation of the JAK2 FERM dimer is required for kinase activation. These data uncover the structural and molecular basis for how a cytokine-bound active receptor dimer brings together two JAK2 molecules to stimulate JAK2 kinase activity. DOI: https://doi.org/10.7554/eLife.38089.001 Introduction Janus kinases (JAKs) are a family of multi-domain non-receptor tyrosine kinases responsible for pleio- tropic regulatory effects on growth, development, immune and hematopoietic signaling (Leonard and O’Shea, 1998). The JAK family consists of four conserved members, including JAK1, *For correspondence: [email protected] JAK2, JAK3, and TYK2, which are differentially activated in response to cytokine and interferon stim- ulation. JAKs are constitutively bound to the intracellular domains of their cognate cytokine signaling Competing interest: See receptors, and are activated after cytokine-mediated dimerization or rearrangement of these recep- page 18 tors establishes a productive receptor signaling complex (Haan et al., 2006).
    [Show full text]
  • Differential Gene Expression in Oligodendrocyte Progenitor Cells, Oligodendrocytes and Type II Astrocytes
    Tohoku J. Exp. Med., 2011,Differential 223, 161-176 Gene Expression in OPCs, Oligodendrocytes and Type II Astrocytes 161 Differential Gene Expression in Oligodendrocyte Progenitor Cells, Oligodendrocytes and Type II Astrocytes Jian-Guo Hu,1,2,* Yan-Xia Wang,3,* Jian-Sheng Zhou,2 Chang-Jie Chen,4 Feng-Chao Wang,1 Xing-Wu Li1 and He-Zuo Lü1,2 1Department of Clinical Laboratory Science, The First Affiliated Hospital of Bengbu Medical College, Bengbu, P.R. China 2Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, P.R. China 3Department of Neurobiology, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China 4Department of Laboratory Medicine, Bengbu Medical College, Bengbu, P.R. China Oligodendrocyte precursor cells (OPCs) are bipotential progenitor cells that can differentiate into myelin-forming oligodendrocytes or functionally undetermined type II astrocytes. Transplantation of OPCs is an attractive therapy for demyelinating diseases. However, due to their bipotential differentiation potential, the majority of OPCs differentiate into astrocytes at transplanted sites. It is therefore important to understand the molecular mechanisms that regulate the transition from OPCs to oligodendrocytes or astrocytes. In this study, we isolated OPCs from the spinal cords of rat embryos (16 days old) and induced them to differentiate into oligodendrocytes or type II astrocytes in the absence or presence of 10% fetal bovine serum, respectively. RNAs were extracted from each cell population and hybridized to GeneChip with 28,700 rat genes. Using the criterion of fold change > 4 in the expression level, we identified 83 genes that were up-regulated and 89 genes that were down-regulated in oligodendrocytes, and 92 genes that were up-regulated and 86 that were down-regulated in type II astrocytes compared with OPCs.
    [Show full text]
  • Pancancer IO360 Human Vapril2018
    Gene Name Official Full Gene name Alias/Prev Symbols Previous Name(s) Alias Symbol(s) Alias Name(s) A2M alpha-2-macroglobulin FWP007,S863-7,CPAMD5 ABCF1 ATP binding cassette subfamily F member 1 ABC50 ATP-binding cassette, sub-family F (GCN20),EST123147 member 1 ACVR1C activin A receptor type 1C activin A receptor, type IC ALK7,ACVRLK7 ADAM12 ADAM metallopeptidase domain 12 a disintegrin and metalloproteinase domainMCMPMltna,MLTN 12 (meltrin alpha) meltrin alpha ADGRE1 adhesion G protein-coupled receptor E1 TM7LN3,EMR1 egf-like module containing, mucin-like, hormone receptor-like sequence 1,egf-like module containing, mucin-like, hormone receptor-like 1 ADM adrenomedullin AM ADORA2A adenosine A2a receptor ADORA2 RDC8 AKT1 AKT serine/threonine kinase 1 v-akt murine thymoma viral oncogene homologRAC,PKB,PRKBA,AKT 1 ALDOA aldolase, fructose-bisphosphate A aldolase A, fructose-bisphosphate ALDOC aldolase, fructose-bisphosphate C aldolase C, fructose-bisphosphate ANGPT1 angiopoietin 1 KIAA0003,Ang1 ANGPT2 angiopoietin 2 Ang2 ANGPTL4 angiopoietin like 4 angiopoietin-like 4 pp1158,PGAR,ARP4,HFARP,FIAF,NL2fasting-induced adipose factor,hepatic angiopoietin-related protein,PPARG angiopoietin related protein,hepatic fibrinogen/angiopoietin-related protein,peroxisome proliferator-activated receptor (PPAR) gamma induced angiopoietin-related protein,angiopoietin-related protein 4 ANLN anillin actin binding protein anillin (Drosophila Scraps homolog), actin bindingANILLIN,Scraps,scra protein,anillin, actin binding protein (scraps homolog, Drosophila)
    [Show full text]
  • Wrap.Warwick.Ac.Uk/91754
    Original citation: Hu, Jiamiao and Christian, Mark. (2017) Hormonal factors in the control of the browning of white adipose tissue. Hormone Molecular Biology and Clinical Investigation. Permanent WRAP URL: http://wrap.warwick.ac.uk/91754 Copyright and reuse: The Warwick Research Archive Portal (WRAP) makes this work by researchers of the University of Warwick available open access under the following conditions. Copyright © and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable the material made available in WRAP has been checked for eligibility before being made available. Copies of full items can be used for personal research or study, educational, or not-for-profit purposes without prior permission or charge. Provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way. Publisher’s statement: “The final publication is available at www.degruyter.com ” http://dx.doi.org/10.1515/hmbci-2017-0017 A note on versions: The version presented here may differ from the published version or, version of record, if you wish to cite this item you are advised to consult the publisher’s version. Please see the ‘permanent WRAP URL’ above for details on accessing the published version and note that access may require a subscription. For more information, please contact the WRAP Team at: [email protected] warwick.ac.uk/lib-publications DE GRUYTER Hormone Molecular Biology and Clinical Investigation.
    [Show full text]
  • Role of the Tyrosine Kinase JAK2 in Signal Transduction by Growth Hormone
    Pediatr Nephrol (2000) 14:550–557 © IPNA 2000 REVIEW ARTICLE Christin Carter-Su · Liangyou Rui James Herrington Role of the tyrosine kinase JAK2 in signal transduction by growth hormone Received: 15 May 1999 / Revised: 23 December 1999 / Accepted: 2 January 2000 Abstract Chronic renal failure in children results in im- Key words Growth · Growth hormone · JAK2 · Insulin paired body growth. This effect is so severe in some receptor substrates · Signal transducers and activators of children that not only does it have a negative impact on transcription · SH2-B their self-image, but it also affects their ability to carry out normal day-to-day functions. Yet the mechanism by which chronic renal failure causes short stature is not Introduction well understood. Growth hormone (GH) therapy increas- es body height in prepubertal children, suggesting that a As early as 1973 [1], growth hormone (GH) was recog- better understanding of how GH promotes body growth nized as binding to a membrane-bound receptor. Yet the may lead to better insight into the impaired body growth mechanism by which GH binding to its receptor elicits in chronic renal failure and therefore better therapies. the diverse responses to GH remained elusive for several This review discusses what is currently known about more decades. Even cloning of the GH receptor [2] in how GH acts at a cellular level. The review discusses 1987 did not shed light on the mechanism by which the how GH is known to bind to a membrane-bound receptor GH receptor functioned, because the deduced amino acid and activate a cytoplasmic tyrosine kinase called Janus sequence of the cloned rabbit and human liver GH recep- kinase (JAK) 2.
    [Show full text]
  • A Bifunctional Fusion Protein Bridging Natural Killer Cells and PRLR-Positive Breast Cancer Cells
    Clemson University TigerPrints All Dissertations Dissertations August 2020 MICA-G129R: A Bifunctional Fusion Protein Bridging Natural Killer Cells and PRLR-positive Breast Cancer Cells Hui Ding Clemson University, [email protected] Follow this and additional works at: https://tigerprints.clemson.edu/all_dissertations Recommended Citation Ding, Hui, "MICA-G129R: A Bifunctional Fusion Protein Bridging Natural Killer Cells and PRLR-positive Breast Cancer Cells" (2020). All Dissertations. 2690. https://tigerprints.clemson.edu/all_dissertations/2690 This Dissertation is brought to you for free and open access by the Dissertations at TigerPrints. It has been accepted for inclusion in All Dissertations by an authorized administrator of TigerPrints. For more information, please contact [email protected]. MICA-G129R: A BIFUNCTIONAL FUSION PROTEIN BRIDGING NATURAL KILLER CELLS AND PRLR-POSITIVE BREAST CANCER CELLS A Dissertation Presented to the Graduate School of Clemson University In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy Biological Sciences by Hui Ding August 2020 Accepted by: Dr. Yanzhang Wei, Committee Chair Dr. Charles D. Rice Dr. Lesly A. Temesvari Dr. Tzuen-Rong Tzeng i ABSTRACT Breast cancer is the most common diagnosed and deathly cancer in women all over the world. Besides the conventional cancer therapy, based on the receptors expressed in breast cancer, hormone therapy targeting estrogen receptors (ER) and progesterone receptors (PR), and targeted therapy using antibodies or inhibitors targeting human epidermal growth factor receptor 2 (HER2) are the common and standard treatments for breast cancer. However, breast cancer is a highly heterogeneous disease. About 15-20% of breast cancers do not significantly express the three receptors, which are classified as the triple-negative breast cancer and the most dangerous type of breast cancer because of lack of effective targets for treatment.
    [Show full text]
  • Role of the B Common (Bc) Family of Cytokines in Health and Disease
    Downloaded from http://cshperspectives.cshlp.org/ on September 28, 2021 - Published by Cold Spring Harbor Laboratory Press Role of the b Common (bc) Family of Cytokines in Health and Disease Timothy R. Hercus,1 Winnie L. T. Kan,1 Sophie E. Broughton,2 Denis Tvorogov,1 Hayley S. Ramshaw,1 Jarrod J. Sandow,3 Tracy L. Nero,2 Urmi Dhagat,2 Emma J. Thompson,1 Karen S. Cheung Tung Shing,2,4 Duncan R. McKenzie,1 Nicholas J. Wilson,5 Catherine M. Owczarek,5 Gino Vairo,5 Andrew D. Nash,5 Vinay Tergaonkar,1,6 Timothy Hughes,1,7 Paul G. Ekert,8 Michael S. Samuel,1,9 Claudine S. Bonder,1 Michele A. Grimbaldeston,1,10 Michael W. Parker,2,4 and Angel F. Lopez1 1The Centre for Cancer Biology, SA Pathology and the University of South Australia, Adelaide, South Australia 5000, Australia 2ACRF Rational Drug Discovery Centre, St. Vincent’s Institute of Medical Research, Fitzroy, Victoria 3065, Australia 3Division of Systems Biologyand Personalised Medicine, The Walter and Eliza Hall Institute; and Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3052, Australia 4Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia 5CSL Limited, Parkville, Victoria 3010, Australia 6Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673, Singapore 7South Australian Health and Medical Research Institute and University of Adelaide, North Terrace, Adelaide, South Australia 5000, Australia 8Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, Victoria 3052, Australia 9School of Medicine, University of Adelaide, Adelaide, South Australia 5000, Australia 10OMNI-Biomarker Development, Genentech Inc., South San Francisco, California 94080 Correspondence: [email protected] The b common ([bc]/CD131) family of cytokines comprises granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5, all of which use bcas their key signaling receptor subunit.
    [Show full text]
  • Janus Kinases in Leukemia
    cancers Review Janus Kinases in Leukemia Juuli Raivola 1, Teemu Haikarainen 1, Bobin George Abraham 1 and Olli Silvennoinen 1,2,3,* 1 Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland; juuli.raivola@tuni.fi (J.R.); teemu.haikarainen@tuni.fi (T.H.); bobin.george.abraham@tuni.fi (B.G.A.) 2 Institute of Biotechnology, Helsinki Institute of Life Science HiLIFE, University of Helsinki, 00014 Helsinki, Finland 3 Fimlab Laboratories, Fimlab, 33520 Tampere, Finland * Correspondence: olli.silvennoinen@tuni.fi Simple Summary: Janus kinase/signal transducers and activators of transcription (JAK/STAT) path- way is a crucial cell signaling pathway that drives the development, differentiation, and function of immune cells and has an important role in blood cell formation. Mutations targeting this path- way can lead to overproduction of these cell types, giving rise to various hematological diseases. This review summarizes pathogenic JAK/STAT activation mechanisms and links known mutations and translocations to different leukemia. In addition, the review discusses the current therapeutic approaches used to inhibit constitutive, cytokine-independent activation of the pathway and the prospects of developing more specific potent JAK inhibitors. Abstract: Janus kinases (JAKs) transduce signals from dozens of extracellular cytokines and function as critical regulators of cell growth, differentiation, gene expression, and immune responses. Deregu- lation of JAK/STAT signaling is a central component in several human diseases including various types of leukemia and other malignancies and autoimmune diseases. Different types of leukemia harbor genomic aberrations in all four JAKs (JAK1, JAK2, JAK3, and TYK2), most of which are Citation: Raivola, J.; Haikarainen, T.; activating somatic mutations and less frequently translocations resulting in constitutively active JAK Abraham, B.G.; Silvennoinen, O.
    [Show full text]
  • FDA Listing of Established Pharmacologic Class Text Phrases January 2021
    FDA Listing of Established Pharmacologic Class Text Phrases January 2021 FDA EPC Text Phrase PLR regulations require that the following statement is included in the Highlights Indications and Usage heading if a drug is a member of an EPC [see 21 CFR 201.57(a)(6)]: “(Drug) is a (FDA EPC Text Phrase) indicated for Active Moiety Name [indication(s)].” For each listed active moiety, the associated FDA EPC text phrase is included in this document. For more information about how FDA determines the EPC Text Phrase, see the 2009 "Determining EPC for Use in the Highlights" guidance and 2013 "Determining EPC for Use in the Highlights" MAPP 7400.13.
    [Show full text]
  • Why Should Growth Hormone (GH) Be Considered a Promising Therapeutic Agent for Arteriogenesis? Insights from the GHAS Trial
    cells Review Why Should Growth Hormone (GH) Be Considered a Promising Therapeutic Agent for Arteriogenesis? Insights from the GHAS Trial Diego Caicedo 1,* , Pablo Devesa 2, Clara V. Alvarez 3 and Jesús Devesa 4,* 1 Department of Angiology and Vascular Surgery, Complejo Hospitalario Universitario de Santiago de Compostela, 15706 Santiago de Compostela, Spain 2 Research and Development, The Medical Center Foltra, 15886 Teo, Spain; [email protected] 3 . Neoplasia and Endocrine Differentiation Research Group. Center for Research in Molecular Medicine and Chronic Diseases (CIMUS). University of Santiago de Compostela, 15782. Santiago de Compostela, Spain; [email protected] 4 Scientific Direction, The Medical Center Foltra, 15886 Teo, Spain * Correspondence: [email protected] (D.C.); [email protected] (J.D.); Tel.: +34-981-800-000 (D.C.); +34-981-802-928 (J.D.) Received: 29 November 2019; Accepted: 25 March 2020; Published: 27 March 2020 Abstract: Despite the important role that the growth hormone (GH)/IGF-I axis plays in vascular homeostasis, these kind of growth factors barely appear in articles addressing the neovascularization process. Currently, the vascular endothelium is considered as an authentic gland of internal secretion due to the wide variety of released factors and functions with local effects, including the paracrine/autocrine production of GH or IGF-I, for which the endothelium has specific receptors. In this comprehensive review, the evidence involving these proangiogenic hormones in arteriogenesis dealing with the arterial occlusion and making of them a potential therapy is described. All the elements that trigger the local and systemic production of GH/IGF-I, as well as their possible roles both in physiological and pathological conditions are analyzed.
    [Show full text]
  • Growth Hormone (GH) and the Cardiovascular System: Studies in Bovine GH
    Growth Hormone (GH) and the Cardiovascular System: Studies in Bovine GH Transgenic and Inducible, Cardiac-Specific GH Receptor Gene Disrupted Mice A dissertation presented to the faculty of the College of Arts and Sciences of Ohio University In partial fulfillment of the requirements for the degree Doctor of Philosophy Adam Jara May 2014 © 2014 Adam Jara. All Rights Reserved. 2 This dissertation titled Growth Hormone (GH) and the Cardiovascular System: Studies in Bovine GH Transgenic and Inducible, Cardiac-Specific GH Receptor Gene Disrupted Mice by ADAM JARA has been approved for the Department of Biological Sciences and the College of Arts and Sciences by John J. Kopchick Distinguished Professor of Molecular Biology and Goll-Ohio Eminent Scholar Robert Frank Dean, College of Arts and Sciences 3 ABSTRACT JARA, ADAM, Ph.D., May 2014, Biological Sciences Growth Hormone (GH) and the Cardiovascular System: Studies in Bovine GH Transgenic and Inducible, Cardiac-Specific GH Receptor Gene Disrupted Mice Director of Dissertation: John J. Kopchick Growth hormone (GH) and insulin-like growth factor I (IGF-I) are thought to play key roles in the development and maintenance of the heart. Evidence of the profound effect GH has on the heart can be found in patients with diseases that disrupt GH action. In pathological states of acromegaly (caused by oversecretion of GH), GH deficiency, and Laron Syndrome (a disease caused by mutations in the GH receptor resulting in systemic lack of GH induced action), patients exhibit unique cardiovascular phenotypes of altered structure and function. Despite these observations, the exact role of GH in the cardiovascular system is not well characterized.
    [Show full text]
  • Growth Hormone in Vascular Pathology: Neovascularization and Expression of Receptors Is Associated with Cellular Proliferation
    ANTICANCER RESEARCH 27: 4201-4218 (2007) Growth Hormone in Vascular Pathology: Neovascularization and Expression of Receptors is Associated with Cellular Proliferation D.T. LINCOLN1, P.K. SINGAL2 and A. AL-BANAW3 1Entity Systems, Independent Research Foundation, 53 Ashburton Street, Chapel Hill QLD 4069, Australia; 2Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Center, Faculty of Medicine, University of Manitoba, Winnipeg, Canada; 3Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Kuwait University, Kuwait Abstract. Vascular tumours are common lesions of the skin contents, duodenum, female breast, abdomen, stomach, colon, and subcutaneous tissue, but also occur in many other tissues lymph node, bladder, body flank and neck regions. The tumours and internal organs. The well-differentiated tumours consist of were of the following pathological entities: Haemangioma irregular anastomosing, blood-filled vascular channels that are (n=12); haemangioendothelioma (n=10); Castleman’s disease lined by variably atypical endothelial cells. The less differentiated (n=3), haemangiopericytoma (n=4); angiosarcoma, (n=11), tumours may show solid strands and sheets, resembling Kaposi’s sarcoma with focal infiltration by lymphoma, HIV +ve carcinoma or lymphoma. Several growth factors, including basic (n=7), Kaposi’s sarcoma (n=17). The endothelial cell marker fibroblast growth factor, transforming growth factors and CD-31 was used to establish endothelial cell characteristics and vascular endothelial
    [Show full text]