DOCSLIB.ORG

Insulin Resistance in Obese Adolescents and Adult Men Modifies the Expression of Proliferation Related Genes

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Insulin Resistance in Obese Adolescents and Adult Men Modifies the Expression of Proliferation Related Genes ISSN 2409-4943. Ukr. Biochem. J., 2019, Vol. 91, N 3 UDC 577.112:616 doi: https://doi.org/10.15407/ubj91.03.065 INSULIN RESISTANCE IN OBESE ADOLESCENTS AND ADULT MEN MODIFIES THE EXPRESSION OF PROLIFERATION RELATED GENES O.N H. MI CHENKO1, Y. M. VILETSKA1,N D. O. MI CHENKO1,2, V. V. DAVYDOV3 1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv; e-mail: [email protected]; 2Bohomolets National Medical University, Kyiv, Ukraine 3SI “Institute of Children and Adolescent Health Care, National Academy of Medical Sciences of Ukraine”, Kharkiv Received: 11 December 2018; Accepted: 14 March 2019 Numerous data demonstrate that key regulatory factors, enzymes and receptors including HSPA5, MEST, SLC1A3, PDGFC, and ADM represent poly-functional, endoplasmic reticulum stress-dependent pro- teins, which control variable metabolic pathways. The expression level of genes of these proteins in the blood and subcutaneous adipose tissue of obese adolescents and adult men with and without insulin resistance was studied. It was shown that in blood of obese adolescents without insulin resistance the expression level of SLC1A3, HSPA5, MEST, and PDGFC genes was significantly increased, but development of insulin resis tance led to down-regulation of these genes expression except HSPA5 gene as compared to the control group as well as to the group of obese adolescents without insulin resistance. At the same time, the expression level of ADM gene did not change significantly in obese adolescents without insulin resistance, but the develop- ment of insulin resistance led to down-regulation of this gene expression. In subcutaneous adipose tissue of obese adult men without insulin resistance the level of SLC1A3 gene expression was decreased, although ADM, MEST, and HSPA5 genes – increased. It was also shown that the development of insulin resistance in obese men affected the expression level of ADM and SLC1A3 genes only. Results of this investigation provide evidence that insulin resistance in obese adolescents and adult men is associated with specific changes in the expression of genes, which related to proliferation and development of obesity and insulin resistance as well as to endoplasmic reticulum stress and contribute to the development of obesity complications. K e y w o r d s: obesity, insulin resistance, gene expression, MEST, HSPA5, ADM, blood, adipose tissue. hildren with severe obesity are at greater bolic syndrome, results from interactions between risk for adult obesity, early atherosclerosis, genes and environmental factors and is associated C hypertension, metabolic syndrome, type 2 with changes in gene expressions of the regulatory diabetes, fatty liver disease and premature death [1]. network in various organs and tissues, but preferen- Thus, childhood obesity is a serious and urgent pub- tially in adipose tissue [5-8]. Adipose tissue growth lic health problem because the number of children is in the center of obesity and tightly associated with with severe obesity is significantly increased [1]. glucose and lipid metabolism as well as cell prolife- The development of obesity, as well as its metabolic ration processes and is controlled by various inter- complications, is associated with dysregulation of connected regulatory factors and enzymes [9]. At numerous intrinsic mechanisms, which control most the same time, the blood reflects numerous changes key metabolic processes, including proliferation, in different organs and tissues in various diseases glucose and lipid metabolism as well as insulin sen- including obesity [10, 11]. Special interest deserves sitivity [2-5]. Furthermore, obesity, as well as meta- the key regulatory factors, which control cell pro- © 2019 Minchenko O. H. et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 65 ISSN 2409-4943. Ukr. Biochem. J., 2019, Vol. 91, N 3 liferation, glucose and lipid metabolism as well as cal processes including embryonic development, an- endoplasmic reticulum stress [2, 4, 8, 12, 13]. Thus, giogenesis, cell proliferation and differentiation, and adolescent obesity is associated with increased ex- contribute to the pathophysiology of some diseases, pression of IRS1, ССN2, IGSEC, RSPO1, IL13RA2, including cancer [27]. It also plays an important role and RIPK2 genes and down-regulated IRS2 and in angiogenesis and blood vessel development, in- DNAJC15 gene expressions, although with insulin duces anti-apoptotic effects on macrophages through resistance is associated the expression IRS1, IRS2, Akt and Bad phosphorylation, but in the nucleus, DNAJC15, RSPO1, and RIPK2 genes only [13]. PDGFC seems to have additional function [17]. Numerous data clearly demonstrate that key Heat shock protein family А member 5 regulatory factors, enzymes and receptors inclu- (HSPA5) is a member of the heat shock protein 70 ding ADM (adrenomedullin), SLC1A3 (solute car- (HSP70) family and is localized in the lumen of the rier family 1, member 3: glial high-affinity gluta- endoplasmic reticulum. It is involved in the correct mate transporter), PDGFC (platelet-derived growth folding and assembly of proteins in the endoplasmic factor C), MEST (mesoderm specific transcript) reticulum as well as in the degradation of misfol- and HSPA5 (heat shock protein family A member ded proteins via its interaction with DNAJC10 [18]. 5) represent poly-functional, endoplasmic reticulum HSPA5 protein is also known as glucose-regulated stress-dependent proteins, which control variable 78kDa protein (GRP78) and immunoglobulin heavy metabolic pathways and are related to oncogenesis chain-binding protein (BiP) as well as endoplasmic [8, 14-19]. Therefore, adrenomedullin is a potent reticulum luminal Ca(2+)-binding protein grp78. It hypotensive peptide, which controls leptin, endothe- is a poly-functional protein, which also presents in lin-1, and adiponectin secretion as well as has re- a nucleus, mitochondrion and extracellular matrix, lation to the development of insulin resistance and participates in the control of various metabolic path- metabolic syndrome [20-23]. Moreover, the increase ways and plays an important role in endoplasmic in leptin and the decrease in adiponectin by ADM reticulum stress, obesity and insulin resistance as in the epididymal fat may have opposite effects on well as in adipogenesis and oncogenesis [18, 28-34]. metabolism [22]. Leptin is an important regulator Thus, the endoplasmic reticulum luminal co-chape- of adipose tissue growth and participates in various rone ERdj4/DNAJB9 is a selective IRE1 repressor signaling pathways including cell proliferation. It is that promotes a complex between the luminal HSP70 interesting to note that ADM is increased in tumors, BiP and the luminal stress-sensing domain of IRE1 promotes metastasis and has relation to oncogenesis [18]. Moreover, recently was shown that p53 targets [14, 15, 23]. Therefore, there is data that ADM and BiP to promote apoptosis during severe endoplasmic erythropoietin receptor may serve as new regulatory reticulum stress and that cell surface BiP/GRP78 fa- factors involved in angiogenesis of hepatocellular cilitates hepatoma cells proliferation and migration carcinoma [24]. by activating IGF-IR [30, 35]. SLC1A3 (solute carrier family 1 member 3) is Next poly-functional gene, which has relation a mitochondrial protein EAAT1 (excitatory amino to obesity, insulin resistance, and cell proliferation, acid transporters 1), which also known as glial high- is MEST (mesoderm specific transcript) [36-38]. affinity glutamate transporter (GLAST1), controls Thus, epigenetic malprogramming of MEST may transport of L-glutamate and also L- and D-aspartate contribute to obesity predisposition throughout life and is essential for terminating the postsynaptic ac- [36]. It is interesting to note that females are more tion of glutamate by rapidly removing released glu- protected from age-related metabolic disturbances, tamate from the synaptic cleft [16, 25, 26]. It is also such as insulin resistance, hepatic lipid deposition, localized in adipocytes and insulin, which coordi- and white adipose tissue inflammation compared to nates the catabolism of nutrients by protein phospho- males. This may be related to their greater capaci- rylation, controls the phosphorylation of the Glu/Asp ty for white adipose tissue expansion-reflected by transporter SLC1A3/EAAT1 in these cells [26]. Re- a greater MEST/LEPTIN mRNA ratio and to their cently was shown that a high-fat diet reduces the hip- ability to maintain adiponectin levels and preserve pocampal content level of lactate which is correlated leptin sensitivity with aging [37]. MEST is a stress with the expression of glial glutamate transporters responsible gene and strongly up-regulated in glio- [25]. Platelet-derived growth factor-C (PDGF-C), ma cells after inhibition of endoplasmic reticulum also known as VEGFE (vascular endothelial growth stress mediated by IRE1 signaling [39]. Moreover, factor E), has roles in the regulation of many biologi- the neuroanatomical and phenotypical consequences 66 O. H. Minchenko, Y. M. Viletska, D. O. Minchenko, V. V. Davydov detected upon the loss of MEST, resemble the loss of vided into three equal groups (7 subjects in each substantia nigra neurons and loss of movement con- group): one group of relative healthy individuals trol as seen in Parkinson's disease,
Load more

Recommended publications
  • Gene Expression Analysis Identifies Potential Biomarkers of Neurofibromatosis Type 1 Including Adrenomedullin
    Published OnlineFirst August 25, 2010; DOI: 10.1158/1078-0432.CCR-10-0613 Clinical Imaging, Diagnosis, Prognosis Cancer Research Gene Expression Analysis Identifies Potential Biomarkers of Neurofibromatosis Type 1 Including Adrenomedullin Trent R. Hummel1, Walter J. Jessen1, Shyra J. Miller1, Lan Kluwe4, Victor F. Mautner4, Margaret R. Wallace5, Conxi Lázaro6, Grier P. Page7, Paul F. Worley8, Bruce J. Aronow2, Elizabeth K. Schorry3, and Nancy Ratner1 Abstract Purpose: Plexiform neurofibromas (pNF) are Schwann cell tumors found in a third of individuals with neurofibromatosis type 1 (NF1). pNF can undergo transformation to malignant peripheral nerve sheath tumors (MPNST). There are no identified serum biomarkers of pNF tumor burden or transformation to MPNST. Serum biomarkers would be useful to verify NF1 diagnosis, monitor tumor burden, and/or detect transformation. Experimental Design: We used microarray gene expression analysis to define 92 genes that encode putative secreted proteins in neurofibroma Schwann cells, neurofibromas, and MPNST. We validated dif- ferential expression by quantitative reverse transcription-PCR, Western blotting, and ELISA assays in cell conditioned medium and control and NF1 patient sera. Results: Of 13 candidate genes evaluated, only adrenomedullin (ADM) was confirmed as differentially expressed and elevated in serum of NF1 patients. ADM protein concentrati on was further elevated in serum of a small sampling of NF1 patients with MPNST. MPNST cell conditioned medium, containing ADM and hepatocyte growth factor, stimulated MPNST migration and endothelial cell proliferation. Conclusions: Thus, microarray analysis identifies potential serum biomarkers for disease, and ADM is a serum biomarker of NF1. ADM serum levels do not seem to correlate with the presence of pNFs but may be a biomarker of transformation to MPNST.
    [Show full text]
  • A Bioinformatics Model of Human Diseases on the Basis Of
    SUPPLEMENTARY MATERIALS A Bioinformatics Model of Human Diseases on the basis of Differentially Expressed Genes (of Domestic versus Wild Animals) That Are Orthologs of Human Genes Associated with Reproductive-Potential Changes Vasiliev1,2 G, Chadaeva2 I, Rasskazov2 D, Ponomarenko2 P, Sharypova2 E, Drachkova2 I, Bogomolov2 A, Savinkova2 L, Ponomarenko2,* M, Kolchanov2 N, Osadchuk2 A, Oshchepkov2 D, Osadchuk2 L 1 Novosibirsk State University, Novosibirsk 630090, Russia; 2 Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia; * Correspondence: [email protected]. Tel.: +7 (383) 363-4963 ext. 1311 (M.P.) Supplementary data on effects of the human gene underexpression or overexpression under this study on the reproductive potential Table S1. Effects of underexpression or overexpression of the human genes under this study on the reproductive potential according to our estimates [1-5]. ↓ ↑ Human Deficit ( ) Excess ( ) # Gene NSNP Effect on reproductive potential [Reference] ♂♀ NSNP Effect on reproductive potential [Reference] ♂♀ 1 increased risks of preeclampsia as one of the most challenging 1 ACKR1 ← increased risk of atherosclerosis and other coronary artery disease [9] ← [3] problems of modern obstetrics [8] 1 within a model of human diseases using Adcyap1-knockout mice, 3 in a model of human health using transgenic mice overexpressing 2 ADCYAP1 ← → [4] decreased fertility [10] [4] Adcyap1 within only pancreatic β-cells, ameliorated diabetes [11] 2 within a model of human diseases
    [Show full text]
  • A Global Transcriptome Analysis Reveals Molecular Hallmarks of Neural Stem Cell Death, Survival, and Differentiation in Response to Partial FGF-2 and EGF Deprivation
    A Global Transcriptome Analysis Reveals Molecular Hallmarks of Neural Stem Cell Death, Survival, and Differentiation in Response to Partial FGF-2 and EGF Deprivation Vanesa Nieto-Este´ vez1,2, Jaime Pignatelli1,2, Marcos J. Arau´ zo-Bravo3, Anahı´ Hurtado-Chong1, Carlos Vicario-Abejo´ n1,2* 1 Instituto Cajal, Consejo Superior de Investigaciones Cientı´ficas (CSIC), Madrid, Spain, 2 Centro de Investigacio´nBiome´dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain, 3 Laboratory of Computational Biology and Bioinformatics, Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Muenster, Germany Abstract Neurosphere cell culture is a commonly used model to study the properties and potential applications of neural stem cells (NSCs). However, standard protocols to culture NSCs have yet to be established, and the mechanisms underlying NSC survival and maintenance of their undifferentiated state, in response to the growth factors FGF-2 and EGF are not fully understood. Using cultures of embryonic and adult olfactory bulb stem cells (eOBSCs and aOBSCs), we analyzed the consequences of FGF-2 and EGF addition at different intervals on proliferation, cell cycle progression, cell death and differentiation, as well as on global gene expression. As opposed to cultures supplemented daily, addition of FGF-2 and EGF every 4 days significantly reduced the neurosphere volume and the total number of cells in the spheres, mainly due to increased cell death. Moreover, partial FGF-2 and EGF deprivation produced an increase in OBSC differentiation during the proliferative phase. These changes were more evident in aOBSC than eOBSC cultures. Remarkably, these effects were accompanied by a significant upregulation in the expression of endogenous Fgf-2 and genes involved in cell death and survival (Cryab), lipid catabolic processes (Pla2g7), cell adhesion (Dscaml1), cell differentiation (Dscaml1, Gpr17, S100b, Ndrg2) and signal transduction (Gpr17, Ndrg2).
    [Show full text]
  • Adrenomedullin Inhibits Hypoxic Cell Death by Upregulation of Bcl-2 in Endometrial Cancer Cells: a Possible Promotion Mechanism for Tumour Growth
    Oncogene (2001) 20, 2937 ± 2945 ã 2001 Nature Publishing Group All rights reserved 0950 ± 9232/01 $15.00 www.nature.com/onc Adrenomedullin inhibits hypoxic cell death by upregulation of Bcl-2 in endometrial cancer cells: a possible promotion mechanism for tumour growth MK Oehler1,3, C Norbury2, S Hague1,3, MCP Rees3 and R Bicknell*,1 1Molecular Angiogenesis Laboratory, Imperial Cancer Research Fund, Institute of Molecular Medicine, John Radclie Hospital, University of Oxford, Oxford, OX3 9DS, UK; 2Cell Cycle Group, University of Oxford, Oxford, OX3 9DS, UK; 3Nueld Department of Obstetrics and Gynaecology, University of Oxford, Oxford, OX3 9DU, UK Regions of hypoxia are a common feature of solid tumours. of benign and malignant tissues and human cancer cell When tumour cells are exposed to hypoxic stress, lines (Hinson et al., 2000). transcription of a battery of genes is initiated. The ADM is a pluripotent peptide with properties angiogenic factor adrenomedullin (ADM) is a hypoxia ranging from inducing vasorelaxation to acting as a regulated gene. ADM is thought to act through the G growth factor for various benign and malignant cell protein-coupled receptor calcitonin receptor-like receptor types (Hinson et al., 2000). We were the ®rst to show (CRLR), with speci®city being conferred by the receptor that ADM is an angiogenic factor (Zhao et al., 1998). associated modifying protein 2 (RAMP2). Here we report Furthermore we demonstrated that ADM expression in for the ®rst time that ADM treated or stably transfected uterine leiomyomas (benign smooth muscle tumours) Ishikawa cells overexpressing ADM show increased correlated with vascular density (Hague et al., 2000).
    [Show full text]
  • Stromal Fibroblasts Present in Breast Carcinomas Promote Tumor Growth
    Stromal fibroblasts present in breast carcinomas promote tumor growth and angiogenesis through adrenomedullin secretion Zohra Benyahia, Nadège Dussault, Mylène Cayol, Romain Sigaud, Caroline Berenguer-Daizé, Christine Delfino, Asma Tounsi, Stéphane Garcia, Pierre-Marie Martin, Kamel Mabrouk, et al. To cite this version: Zohra Benyahia, Nadège Dussault, Mylène Cayol, Romain Sigaud, Caroline Berenguer-Daizé, et al.. Stromal fibroblasts present in breast carcinomas promote tumor growth and angiogenesis through adrenomedullin secretion. Oncotarget, Impact journals, 2017, 8 (9), 10.18632/oncotarget.14999. hal-01699152 HAL Id: hal-01699152 https://hal-amu.archives-ouvertes.fr/hal-01699152 Submitted on 2 Feb 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. www.impactjournals.com/oncotarget/ Oncotarget, 2017, Vol. 8, (No. 9), pp: 15744-15762 Research Paper Stromal fibroblasts present in breast carcinomas promote tumor growth and angiogenesis through adrenomedullin secretion Zohra Benyahia1, Nadège Dussault1, Mylène Cayol1, Romain Sigaud1, Caroline Berenguer-Daizé1,
    [Show full text]
  • Biomarkers in Community-Acquired Pneumonia: Still Searching for the One
    EDITORIAL | RESPIRATORY INFECTION Biomarkers in community-acquired pneumonia: still searching for the one Oriol Sibila 1,2 and Marcos I. Restrepo3 Affiliations: 1Servei de Pneumologia, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 2Institut d´Investigació Biomèdica Sant Pau (IIB Sant Pau), Barcelona, Spain. 3Division of Pulmonary Diseases and Critical Care Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. Correspondence: Oriol Sibila, Servei de Pneumologia, Hospital de la Santa Creu i Sant Pau, C/ Sant Antoni M. Claret 167, 08025 Barcelona, Spain. E-mail: [email protected] @ERSpublications Fibroblast growth factor 21 (FGF21) predicts severity of illness, clinical stability and mortality in community-acquired pneumonia. Validation is needed to confirm the application of FGF21 in clinical practice. http://ow.ly/SYI730nuRc1 Cite this article as: Sibila O, Restrepo MI. Biomarkers in community-acquired pneumonia: still searching for the one. Eur Respir J 2019; 53: 1802469 [https://doi.org/10.1183/13993003.02469-2018]. Community-acquired pneumonia (CAP) remains a major cause of morbidity and mortality worldwide [1]. Despite advances in antibiotic treatment and medical care, the mortality of CAP is still high in hospitalised patients, especially in those with severe illness [2]. Appropriate initial severity assessment is a crucial step in pneumonia management, since it has been demonstrated that an early recognition of severe CAP patients improves their clinical outcomes [3]. Several tools have been developed to evaluate disease severity, in particular focusing on predicting hospital admission and mortality [4]. However, recent studies have showed that most of these scores are not used routinely in clinical practice and may be inadequate tools to guide appropriate antibiotic treatment [5, 6].
    [Show full text]
  • Adrenomedullin Antagonist Suppresses Tumor Formation in Renal
    1379-1386.qxd 16/4/2010 10:31 Ì ™ÂÏ›‰·1379 INTERNATIONAL JOURNAL OF ONCOLOGY 36: 1379-1386, 2010 Adrenomedullin antagonist suppresses tumor formation in renal cell carcinoma through inhibitory effects on tumor endothelial cells and endothelial progenitor mobilization KUNIHIKO TSUCHIYA1,2,3,4*, KYOKO HIDA2*, YASUHIRO HIDA5, CHIKARA MURAKI2,3, NORITAKA OHGA2,3, TOMOSHIGE AKINO2,3,4, TAKESHI KONDO4, TETSUYA MISEKI1, KOJI NAKAGAWA1, MASANOBU SHINDOH3, TORU HARABAYASHI4, NOBUO SHINOHARA4, KATSUYA NONOMURA4 and MASANOBU KOBAYASHI1,7 1Division of Cancer Biology, Institute for Genetic Medicine, Hokkaido University; 2Division of Vascular Biology, 3Division of Oral Pathobiology, Hokkaido University, Graduate School of Dental Medicine; 4Department of Urology, 5Department of Surgical Oncology, 6Department of Gastroenterology and Hematology, Hokkaido University, Graduate School of Medicine; 7School of Nursing & Social Services, Health Sciences University of Hokkaido, Sapporo, Japan Received November 26, 2009; Accepted January 25, 2010 DOI: 10.3892/ijo_00000622 Abstract. Adrenomedullin (AM) is a multifunctional 52-amino (EPC) into circulation was inhibited by AMA. These results acid peptide. AM has several effects and acts as a growth suggest that AMA can be considered a good anti-angiogenic factor in several types of cancer cells. Our previous study reagent that selectively targets TECs and EPC in renal revealed that an AM antagonist (AMA) suppressed the cancer. growth of pancreatic tumors in mice, although its mechanism was not elucidated. In this study, we constructed an AMA Introduction expression vector and used it to treat renal cell carcinoma (RCC) in mice. This AMA expression vector significantly Renal cell carcinoma (RCC) is a refractory cancer, and cyto- reduced tumor growth in mice.
    [Show full text]
  • Adrenomedullin in Dental Tissues
    Adrenomedullin in Dental Tissues by David Musson A thesis submitted to the Faculty of Medicine and Dentistry of the University of Birmingham for the degree of Doctor of Philosophy School of Dentistry The University of Birmingham June 2010 University of Birmingham Research Archive e-theses repository This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. Abstract Tooth development is complex and dependent on epithelial-mesenchymal interactions involving key molecular signalling pathways. Preliminary data indicate that the pleiotropic growth factor adrenomedullin (ADM) is expressed during tooth development. Furthermore, in osteoblasts, cells which share structural and functional similarities to odontoblasts, ADM increases proliferation in vitro and can promote mineralised bone volume and strength in vivo. Immunohistochemical analysis of ADM demonstrated expression during key stages in tooth development in particular in cells responsible for signalling odontoblast differentiation and subsequently in secretory odontoblasts. Similarities with the temporo-spatial expression profile of TGF-β1 were also observed. In vitro analysis using the developmentally derived dental cell lines, MDPC-23 and OD-21, demonstrated ADM stimulated a biphasic response in dental cell numbers with peak stimulation at 10-11M and that it stimulated mineral deposition at levels comparable to that of the known mineralising agent dexamethasone.
    [Show full text]
  • Table S1. List of All Proteins Included in the Proseek® Multiplex Oncology I V2 96X96 Cancer Panel
    Table S1. List of all proteins included in the Proseek® Multiplex Oncology I v2 96x96 Cancer Panel. Adrenomedullin (AM) Ezrin (EZR) Latency-associated peptide transforming growth factor beta-1 (LAP TGF-beta-1) Amphiregulin (AR) Fas antigen ligand (FasL) Angiopoietin-1 receptor (TIE2) FAS-associated death domain protein (FADD) Lipopolysaccharide-induced tumor necrosis factor- alpha factor (LITAF) B-cell activating factor (BAFF) Fms-related tyrosine kinase 3 ligand (Flt3L) Cadherin-3 (CDH3) Folate receptor alpha (FR-alpha) Macrophage colony-stimulating factor 1 (CSF-1) Carbonic anhydrase IX (CAIX) Follistatin (FS) Matrix metalloproteinase-1 (MMP-1) Carcinoembryonic antigen (CEA) Furin (FUR) Melanoma-derived growth regulatory protein (MIA) Caspase-3 (CASP-3) Growth hormone (GH) MHC class I polypeptide-related sequence A (MIC-A) C-C motif chemokine 19 (CCL19) Growth/differentiation factor 15 (GDF-15) Midkine (MK) CD40 ligand (CD40-L) Heparin-binding EGF-like growth factor (HB-EGF) Monocyte chemotactic protein 1 (MCP-1) C-X-C motif chemokine 5 (CXCL5) Hepatocyte growth factor (HGF) Myeloid differentiation primary response protein MyD88 (MYD88) C-X-C motif chemokine 9 (CXCL9) ICOS ligand (ICOSLG) C-X-C motif chemokine 10 (CXCL10) Immunoglobulin-like transcript 3 (ILT-3) NF-kappa-B essential modulator (NEMO) C-X-C motif chemokine 11 (CXCL11) Integrin alpha-1 (ITGA1) NT-3 growth factor receptor (NTRK3) C-X-C motif chemokine 13 (CXCL13) Interferon gamma (IFN-gamma) Ovarian cancer-related tumor marker CA 125 (CA-125) Cyclin-dependent kinase inhibitor
    [Show full text]
  • Expression of Adrenomedullin in Rats After Spinal Cord Injury and Intervention Effect of Recombinant Human Erythropoietin
    3680 EXPERIMENTAL AND THERAPEUTIC MEDICINE 12: 3680-3684, 2016 Expression of adrenomedullin in rats after spinal cord injury and intervention effect of recombinant human erythropoietin LIANG ZHAO1, YU JING2, LIN QU1, XIANGWEI MENG1, YANG CAO1 and HUIBING TAN3 Departments of 1Orthopeadic Surgery and 2General Surgery, The First Affiliated Hospital of Jinzhou Medical University; 3Department of Anatomy Teaching and Research, Jinzhou Medical University, Jinzhou, Liaoning 121000, P.R. China Received May 13, 2016; Accepted September 19, 2016 DOI: 10.3892/etm.2016.3832 Abstract. The expression of adrenomedullin (ADM) in sharing homology with calcitonin gene-related peptide and injured tissue of rat spinal cord was observed and the effect of has functions of vascular dilation and diuretic activity (2). In a recombinant human erythropoietin was analyzed. A total of healthy individual, a considerable plasmatic concentration of 45 Sprague-Dawley rats were selected and divided into 3 equal ADM is involved in the regulation of plasma (3). In addition, groups including, a sham-operation group in which rats received as a bioactive peptide, ADM has extensive biological functions an excision of vertebral plate; a spinal cord injury model group and is distributed in almost all tissues (4), particularly in and a recombinant human erythropoietin group in which normal adrenal medulla, heart, lung, kidney, blood plasma, rats with spinal cord injury received a caudal vein injection and urine and is able to reduce high blood pressure, dilate of 300 units recombinant human erythropoietin after injury. blood vessels, pulmonary and renal arteries, and relieve Hematoxylin and eosin staining was performed to observe the bronchospasms (5).
    [Show full text]
  • Reduced Maternal Expression of Adrenomedullin Disrupts Fertility, Placentation, and Fetal Growth in Mice Manyu Li,1 Della Yee,2 Terry R
    Research article Reduced maternal expression of adrenomedullin disrupts fertility, placentation, and fetal growth in mice Manyu Li,1 Della Yee,2 Terry R. Magnuson,2 Oliver Smithies,3 and Kathleen M. Caron1,2 1Department of Cell and Molecular Physiology, 2Department of Genetics, and 3Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. Adrenomedullin (AM) is a multifunctional peptide vasodilator that is essential for life. Plasma AM expression dramatically increases during pregnancy, and alterations in its levels are associated with complications of preg- nancy including fetal growth restriction (FGR) and preeclampsia. Using AM+/– female mice with genetically reduced AM expression, we demonstrate that fetal growth and placental development are seriously compro- mised by this modest decrease in expression. AM+/– female mice had reduced fertility characterized by FGR. The incidence of FGR was also influenced by the genotype of the embryo, since AM–/– embryos were more often affected than either AM+/– or AM+/+ embryos. We demonstrate that fetal trophoblast cells and the mater- nal uterine wall have coordinated and localized increases in AM gene expression at the time of implantation. Placentas from growth-restricted embryos showed defects in trophoblast cell invasion, similar to defects that underlie human preeclampsia and placenta accreta. Our data provide a genetic in vivo model to implicate both maternal and, to a lesser extent, embryonic levels of AM in the processes of implantation, placentation, and subsequent fetal growth. This study provides the first genetic evidence to our knowledge to suggest that a mod- est reduction in human AM expression during pregnancy may have an unfavorable impact on reproduction.
    [Show full text]
  • Adrenomedullin Expression Characterizes Leukemia Stem Cells and Associates with an Inflammatory Signature in Acute Myeloid Leukemia
    ORIGINAL RESEARCH published: 02 June 2021 doi: 10.3389/fonc.2021.684396 Adrenomedullin Expression Characterizes Leukemia Stem Cells and Associates With an Inflammatory Signature in Acute Myeloid Leukemia Giorgia Simonetti 1*,DavideAngeli 2, Elisabetta Petracci 2,EugenioFonzi 2,SusannaVedovato 3, Alessandra Sperotto 4, Antonella Padella 1, Martina Ghetti 1, Anna Ferrari 1, Valentina Robustelli 5,6, Rosa Di Liddo 7, Maria Teresa Conconi 7, Cristina Papayannidis 5, Claudio Cerchione 8, Michela Rondoni 9, Annalisa Astolfi 10,11, Emanuela Ottaviani 5, Giovanni Martinelli 12 and Michele Gottardi 13 Edited by: 1 Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy, 2 Unit of Alessandro Isidori, Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy, AORMN Hospital, Italy 3 Department of Clinical and Experimental Medicine, University of Padova, Padua, Italy, 4 Hematology and Transplant Center Reviewed by: Unit, Dipartimento di Area Medica (DAME), Udine University Hospital, Udine, Italy, 5 IRCCS Azienda Ospedaliero-Universitaria Adria´ n Mosquera Orgueira, di Bologna, Istituto di Ematologia “Seràgnoli”, Bologna, Italy, 6 Dipartimento di Medicina Specialistica, Diagnostica e University Hospital of Santiago de Sperimentale, Università di Bologna, Bologna, Italy, 7 Department of Pharmaceutical and Pharmacological Sciences, Compostela, Spain University of Padova, Padua, Italy, 8 Hematology Unit, IRCCS Istituto Romagnolo per
    [Show full text]