DOCSLIB.ORG

Etude Des Mécanismes D'actions De Supermapo Dans Un Modèle De

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Etude Des Mécanismes D'actions De Supermapo Dans Un Modèle De Etude des mécanismes d’actions de SuperMApo dans un modèle de sclérose en plaques Thierry Gauthier To cite this version: Thierry Gauthier. Etude des mécanismes d’actions de SuperMApo dans un modèle de sclérose en plaques. Immunologie. Université Bourgogne Franche-Comté, 2017. Français. NNT : 2017UBFCE010. tel-02319441 HAL Id: tel-02319441 https://tel.archives-ouvertes.fr/tel-02319441 Submitted on 18 Oct 2019 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. « Université de Bourgogne Franche-Comté UFR des Sciences Médicales et Pharmaceutiques » Ecole doctorale Environnements-Santé Etude des mécanismes d’actions de SuperMApo dans un modèle de sclérose en plaques Thèse Présentée et soutenue publiquement le 17 Octobre 2017 par Thierry Gauthier En vue du grade de Docteur de l’Université de Bourgogne Franche -Comté Spécialité : Sciences de la vie et de la santé Travaux réalisés au sein de l’UMR1098 Interactions Hôte -Greffon-Tumeur, ingénierie cellulaire et génique (EFS BFC/INSERM) à Besançon Directeur de thèse : Dr. Sylvain Perruche Jury : Pr. Stéphanie Hugues Rapporteur Université de Genève Pr. Régis Josien Rapporteur Université de Nantes Pr. Christophe Baron (Président du Jury) Examinateur Université de Tours Dr. Eric Hervouet Examinateur Université de Bourgogne Franche-Comté Dr. Sylvain Perruche Examinateur Université de Bourgogne Franche-Comté Remerciements Je souhaite en premier lieu remercier les Pr Stéphanie Hugues et Régis Josien pour avoir accepté d’évaluer mon manuscrit de thèse ainsi que de faire partie de mon jury de thèse. Je remercie également le Pr Christophe Baron et le Dr Eric Hervouet pour leurs conseils tout au long de ce projet au sein du comité de suivi de thèse et leur participation à mon jury de thèse. Je tiens tout particulièrement à remercier le Dr Sylvain Perruche pour m’avoir donné la chance de trouver une thèse et m’avoir fait confiance durant ces trois années. Malgré les nombreuses difficultés tu m’as toujours soutenu et relancer lorsque rien ne marchait. Merci pour ton expertise, tes encouragements, ton amitié et m’avoir permis de trouver ma voie (dans la recherche bien sûr pas dans l’enseignement). Et surtout merci pour cette immense opportunité de post-doc que je te dois en grande partie (pour ne pas dire plus) . J’espère que nous continuerons à collaborer durant de nombreuses années. Je remercie aussi le Pr Philippe Saas pour m’avoir accueilli au sein de s on équipe de recherche et pour vos conseils toujours précieux. Je remercie également l’EFS, le LIPSTIC et l’université de Bourgogne Franche -Comté pour leur soutien financier durant ces trois années de thèse. Je voulais également remercier l’ensemble de membre de l’ex EA3922 (Michaël, Régis, Gilles, Annick, Pascale, Hélène, Jean) pour avoir permis à de nombreuses génération d’étudiants de devenir ce qu’ils sont, pour m’avoir permis d’intégrer votre laboratoire et de découvrir ce qu’était la recherche. Merci à toi Eric pour m’avoir encadré avec Michaël durant ces deux années merveilleuses. Merci pour votre amitié, vos nombreux conseils, votre dynamisme et vos encouragements qui me permettront à n’en pas douter de devenir un grand chercheur (et accessoirement d’être un super lanceur de falcon 15). Merci à Laura et Aurore mes deux thésardes préférées qui ont toujours été d’une gentillesse immense et d’une grande aide au labo (P.S : La team Hervouet…). A toutes les personnes à l’UMR1098 qui ont été nécessaires à la réalisation de ce travail : Anna pour ta bonne humeur, tes inventions géniales (à mon goût en tout cas), ton aide matinale et tardive sur mes nombreuses manips et tout simplement d’être Banana. Un jour tu deviendras riche et célèbre grâce à une de tes inventions… Cécile, Anaïs et Hanane : la dream team du bureau du haut (qui riez toujours à mes blagues… ou pas du tout). Cécile merci pour toutes ces manips où je t’ai levé au petit matin un peu trop tôt, pour les fois innombrables ou tu auras vu une présentation brillante sur le SuperMApo. Et non ne t’inquiète pas tu n’as pas les cheveux de M….. Le P.. Yo Anaïs, ça va ? Un jour tu maniperas une semaine entière sans venir la nuit, un jour. Bon par contre les cicatrices chéloïdes non mais sérieusement ??? Hanane merci pour ta bonne humeur, ta gentillesse et surto ut merci d’avoir corrigé ma thèse. Finalement tu es un peu mon co - directeur de thèse maintenant. Ah oui et merci pour tous les midis où tu as mangé avec nous. Mélanie, toi qui est un peu la Super(women)MApo du laboratoire, merci pour tes nombreux conseils, ta gentillesse, ta bonne humeur et surtout ton supercookie géant. Bonne chance pour ton futur poste de directrice de production de medinn’ pharma. Francis, merci pour tes nombreux conseils qui m’ont été d’un grand secours au laboratoire (tri de pDC J). J’espère un jour devenir un aussi grand manipulateur de souris que toi (PRO sans les endormir entre autre). Martine, ma compagne de recherche, merci pour ton aide précieuse au cours de ces 5 années et ses nombreux sacrifices d’intestin de souris à 7h du mati n. Ne déprime pas trop l’Angleterre ça à l’air cool et puis on peut faire des Immunity là bas… Mymi et Alphonsine, merci pour votre bonne humeur, votre gentillesse, toute votre aide qui ont rendu les difficultés administratives bien plus sympathiques. Mon petit bichon d’amour (alias Adam Ceroi), que la vie est triste ici sans tes blagues de mauvais goût et ta folie scientifique. En tout cas j’espère que je serai le parrain du petit LymphoJedi qui naîtra un jour avec Laurie. Ah oui et ne la laisse pas partir celle-là tu ne retrouveras une femme jamais d’aussi formidable (déjà que c’est dur à la base mais pour toi…). Idir, pour sa grande amitié durant ces trois années. Séverine, Inès, Kiki (la petite jeune), Sami, Anaïs, Dom, François, Emmanuel, Emilie, Pacou, Charline, Sophie et Romain pour avoir partagé votre quotidien et de bons moments avec moi à l’IBCT. A toutes les personnes travaillant à l’EFS pour leur aide, leur gentillesse et leur amitié : Emilie et Sindy mes dernières camarades survivantes de la licence, Walid, Clémence, Jeanne, Sarah, Clémentine, Anne, Sabeha, Jean-René, Jean-Marie, Jean-Paul, Elodie, Laurie, Caroline, Yann, Olivier. Je tiens également à remercier chaleureusement ma famille et plus particulièrement mes parents. Merci pour tout (votre éducation, votre amour, votre soutien et votre rôle dans cette thèse). Je ne peux malheureusement pas m’étendre mais sachez que je vous dois tout et que je vous serai à jamais reconnaissant. Sabrioche, qui est là depuis plus de 10 ans déjà (mais qui m’a q uand même abandonné malgré tout…). Enfin, à mon petit cœur, mon Amour, Ranya. Tu as toujours été là pour moi depuis 5 ans pour me soutenir, m’aider, me rendre heureux même quand j’étais insupportable. Merci de m’avoir donné les 3 enfants les plus merveilleux du monde. J’espère qu’un jour je deviendrai un mari aussi exceptionnel que tu le mérites. Sache que la plus grande réussite de ma vie c’est vous et que cette thèse est d’abord la tienne car elle n’aurait jamais été sans toi. Liste des abréviations ................................................................................................................. 4 Résumé ....................................................................................................................................... 6 Introduction ................................................................................................................................ 7 La réponse inflammatoire ........................................................................................................... 8 I) Concept général .................................................................................................................. 8 I.1) Définition ......................................................................................................................... 8 I.2) La réponse inflammatoire, un processus en deux étapes ................................................. 8 I.3) Initiation de la réponse inflammatoire ........................................................................... 10 I.3.1) Les inducteurs exogènes ......................................................................................... 10 I.3.2. Les inducteurs endogènes ....................................................................................... 11 I.3.3 Les récepteurs aux inducteurs .................................................................................. 11 I.3.4) Les médiateurs solubles de l’inflammation ............................................................ 15 I.3.5) Les médiateurs cellulaires de la réponse inflammatoire ......................................... 16 Les neutrophiles : un effecteur essentiel de la réponse inflammatoire ............................ 16 II) La résolution de l’inflammation ...................................................................................... 20 II.1) Les macrophages, acteurs essentiels de la résolution de l’inflammation ................. 20 II.2) L’efferocytose .........................................................................................................
Load more

Recommended publications
  • Epigenetic Repression of RARRES1 Is Mediated by Methylation of a Proximal Promoter and a Loss of CTCF Binding
    Epigenetic Repression of RARRES1 Is Mediated by Methylation of a Proximal Promoter and a Loss of CTCF Binding Zhengang Peng1,2, Rulong Shen3, Ying-Wei Li1,2, Kun-Yu Teng1,2, Charles L. Shapiro4, Huey-Jen L. Lin1,2,5* 1 Division of Medical Technology, School of Allied Medical Professions, the Ohio State University Medical Center, Columbus, Ohio, United States of America, 2 Molecular Biology and Cancer Genetics Program, Comprehensive Cancer Center, the Ohio State University Medical Center, Columbus, Ohio, United States of America, 3 Department of Pathology, the Ohio State University Medical Center, Columbus, Ohio, United States of America, 4 Department of Medical Oncology, the Ohio State University Medical Center, Columbus, Ohio, United States of America, 5 Department of Medical Technology, University of Delaware, Newark, Delaware, United States of America Abstract Background: The cis-acting promoter element responsible for epigenetic silencing of retinoic acid receptor responder 1 (RARRES1) by methylation is unclear. Likewise, how aberrant methylation interplays effectors and thus affects breast neoplastic features remains largely unknown. Methodology/Principal Findings: We first compared methylation occurring at the sequences (2664,+420) flanking the RARRES1 promoter in primary breast carcinomas to that in adjacent benign tissues. Surprisingly, tumor cores displayed significantly elevated methylation occurring solely at the upstream region (2664,286), while the downstream element (285,+420) proximal to the transcriptional start site (+1) remained largely unchanged. Yet, hypermethylation at the former did not result in appreciable silencing effect. In contrast, the proximal sequence displayed full promoter activity and methylation of which remarkably silenced RARRES1 transcription. This phenomenon was recapitulated in breast cancer cell lines, in which methylation at the proximal region strikingly coincided with downregulation.
    [Show full text]
  • Genetic and Epigenetic Profiling of Human Prostate Cancer Cell-Subsets
    Genetic and Epigenetic Profiling of Human Prostate Cancer Cell-Subsets Alberto John Taurozzi PhD University of York Biology September 2016 Abstract Perturbation of androgen signalling drives progression of human prostate cancer (CaP) to castration-resistant prostate cancer (CRPC). Additionally, CaP is initiated and maintained by cancer stem cells (CSC)s which are analogous to normal prostate stem cells (SC)s. This study presents a qPCR assay to detect androgen receptor gene amplification (GAAR), which is the most common mechanism of castration resistance (>30%). Also, the epigenetic regulation and function of two SC-silenced genes with tumour-suppressive activity (Latexin (LXN) and Retinoic Acid Receptor Responder 1 (RARRES1)) were interrogated using micro-ChIP, transcriptional profiling and mass spectrometry. Traditionally, GAAR is detected using FISH which is labour-intensive and semi- quantitative, limiting clinical applicability. The mechanism of action of LXN or RARRES1 in CaP is unknown, and epigenetic regulation by DNA methylation has been ruled-out in primary CaP. The qPCR assay can detect GAAR in minor cell populations (~1%) within a heterogeneous sample and also quantifies X chromosome aneuploidy (XCA) - a predictor of poor- prognosis in CaP. GAAR and XCA were detected in near-patient xenografts derived from CRPC-tissue indicating that these abnormalities are present in cells capable of in vivo tumour-reconstitution. Micro-ChIP analysis of fractionated primary CaP cultures identified bivalent chromatin at LXN and RARRES1 promoters. Transcriptomic profiling failed to reveal significant changes in gene expression after transduction with LXN or RARRES1. However, an interactome for LXN and RARRES1 was successfully generated in PC3 cells. Additionally, confocal microscopy of mVenus-tagged LXN revealed a pan-cellular distribution which is reflected in the interactome.
    [Show full text]
  • Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
    Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase
    [Show full text]
  • Breast Cancer Subtype Dictates DNA Methylation and ALDH1A3- Mediated Expression of Tumor Suppressor RARRES1
    www.impactjournals.com/oncotarget/ Oncotarget, Vol. 7, No. 28 Research Paper Breast cancer subtype dictates DNA methylation and ALDH1A3- mediated expression of tumor suppressor RARRES1 Krysta M. Coyle1, J. Patrick Murphy2, Dejan Vidovic1, Ahmad Vaghar-Kashani1,3, Cheryl A. Dean1,2, Mohammad Sultan1, Derek Clements1, Melissa Wallace2, Margaret L. Thomas1, Amos Hundert4, Carman A. Giacomantonio1,5, Lucy Helyer5, Shashi A. Gujar1,2,6, Patrick W.K. Lee1,2, Ian C.G. Weaver4, Paola Marcato1 1Department of Pathology, Dalhousie University, Halifax, NS, Canada 2Department of Microbiology & Immunology, Dalhousie University, Halifax, NS, Canada 3Department of Biology Education Center, Uppsala University, Uppsala, Sweden 4Department of Psychology and Neuroscience, and Psychiatry, Dalhousie University, Halifax, NS, Canada 5Department of Surgery, Dalhousie University, Halifax, NS, Canada 6Department of Quality and System Performance, IWK Health Centre, Halifax, NS, Canada Correspondence to: Paola Marcato, email: [email protected] Keywords: breast cancer, RARRES1, retinoic acid, ALDH1A3, DNA methylation Received: March 30, 2016 Accepted: May 09, 2016 Published: June 06, 2016 ABSTRACT Breast cancer subtyping, based on the expression of hormone receptors and other genes, can determine patient prognosis and potential options for targeted therapy. Among breast cancer subtypes, tumors of basal-like and claudin-low subtypes are typically associated with worse patient outcomes, are primarily classified as triple- negative breast cancers (TNBC), and cannot be treated with existing hormone- receptor-targeted therapies. Understanding the molecular basis of these subtypes will lead to the development of more effective treatment options for TNBC. In this study, we focus on retinoic acid receptor responder 1 (RARRES1) as a paradigm to determine if breast cancer subtype dictates protein function and gene expression regulation.
    [Show full text]
  • Tumor Suppressor RARRES1 Interacts with Cytoplasmic Carboxypeptidase AGBL2 to Regulate the A-Tubulin Tyrosination Cycle
    Published OnlineFirst February 8, 2011; DOI: 10.1158/0008-5472.CAN-10-2294 Cancer Priority Report Research Tumor Suppressor RARRES1 Interacts with Cytoplasmic Carboxypeptidase AGBL2 to Regulate the a-Tubulin Tyrosination Cycle Ziad J. Sahab1, Michael D. Hall1, You Me Sung1, Sivanesan Dakshanamurthy1, Yun Ji1, Deepak Kumar2, and Stephen W. Byers1,2 Abstract Even though it is among the most commonly methylated loci in multiple cancers, the retinoic acid–induced tumor suppressor retinoic acid receptor responder 1 (RARRES1) has no known function. We now show that RARRES1 is lost in many cancer cells, particularly those with a mesenchymal phenotype, and is a transmem- brane carboxypeptidase inhibitor that interacts with ATP/GTP binding protein-like 2 (AGBL2), a cytoplasmic carboxypeptidase. Knockdown of AGBL2 results in a failure of the cell to detyrosinate the C-terminal EEY region of a-tubulin and indicates that it is a candidate for the long sought-after tubulin tyrosine carboxypeptidase important in the regulation of microtubule dynamics. In contrast, knockdown of RARRES1 increases the level of detyrosinated a-tubulin consistent with a role as the cognate inhibitor of AGBL2. We conclude that RARRES1, its interacting partners AGBL2, Eg5/KIF11, another EEY-bearing protein (EB1), and the microtubule tyrosination cycle are important in tumorigenesis and identify a novel area for therapeutic intervention. Cancer Res; 71(4); 1219–28. Ó2011 AACR. Introduction trolling aspects of stem cell biology, in which an inverse and direct relationship between LXN expression and the size of the Retinoic acid receptor responder 1 (RARRES1), also known hematopoietic stem cell population in mice has been reported as tazarotene-induced gene 1, was first identified as a novel (4).
    [Show full text]
  • ID AKI Vs Control Fold Change P Value Symbol Entrez Gene Name *In
    ID AKI vs control P value Symbol Entrez Gene Name *In case of multiple probesets per gene, one with the highest fold change was selected. Fold Change 208083_s_at 7.88 0.000932 ITGB6 integrin, beta 6 202376_at 6.12 0.000518 SERPINA3 serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 3 1553575_at 5.62 0.0033 MT-ND6 NADH dehydrogenase, subunit 6 (complex I) 212768_s_at 5.50 0.000896 OLFM4 olfactomedin 4 206157_at 5.26 0.00177 PTX3 pentraxin 3, long 212531_at 4.26 0.00405 LCN2 lipocalin 2 215646_s_at 4.13 0.00408 VCAN versican 202018_s_at 4.12 0.0318 LTF lactotransferrin 203021_at 4.05 0.0129 SLPI secretory leukocyte peptidase inhibitor 222486_s_at 4.03 0.000329 ADAMTS1 ADAM metallopeptidase with thrombospondin type 1 motif, 1 1552439_s_at 3.82 0.000714 MEGF11 multiple EGF-like-domains 11 210602_s_at 3.74 0.000408 CDH6 cadherin 6, type 2, K-cadherin (fetal kidney) 229947_at 3.62 0.00843 PI15 peptidase inhibitor 15 204006_s_at 3.39 0.00241 FCGR3A Fc fragment of IgG, low affinity IIIa, receptor (CD16a) 202238_s_at 3.29 0.00492 NNMT nicotinamide N-methyltransferase 202917_s_at 3.20 0.00369 S100A8 S100 calcium binding protein A8 215223_s_at 3.17 0.000516 SOD2 superoxide dismutase 2, mitochondrial 204627_s_at 3.04 0.00619 ITGB3 integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61) 223217_s_at 2.99 0.00397 NFKBIZ nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, zeta 231067_s_at 2.97 0.00681 AKAP12 A kinase (PRKA) anchor protein 12 224917_at 2.94 0.00256 VMP1/ mir-21likely ortholog
    [Show full text]
  • Downregulation of SNRPG Induces Cell Cycle Arrest and Sensitizes Human Glioblastoma Cells to Temozolomide by Targeting Myc Through a P53-Dependent Signaling Pathway
    Cancer Biol Med 2020. doi: 10.20892/j.issn.2095-3941.2019.0164 ORIGINAL ARTICLE Downregulation of SNRPG induces cell cycle arrest and sensitizes human glioblastoma cells to temozolomide by targeting Myc through a p53-dependent signaling pathway Yulong Lan1,2*, Jiacheng Lou2*, Jiliang Hu1, Zhikuan Yu1, Wen Lyu1, Bo Zhang1,2 1Department of Neurosurgery, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen 518020, China;2 Department of Neurosurgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China ABSTRACT Objective: Temozolomide (TMZ) is commonly used for glioblastoma multiforme (GBM) chemotherapy. However, drug resistance limits its therapeutic effect in GBM treatment. RNA-binding proteins (RBPs) have vital roles in posttranscriptional events. While disturbance of RBP-RNA network activity is potentially associated with cancer development, the precise mechanisms are not fully known. The SNRPG gene, encoding small nuclear ribonucleoprotein polypeptide G, was recently found to be related to cancer incidence, but its exact function has yet to be elucidated. Methods: SNRPG knockdown was achieved via short hairpin RNAs. Gene expression profiling and Western blot analyses were used to identify potential glioma cell growth signaling pathways affected by SNRPG. Xenograft tumors were examined to determine the carcinogenic effects of SNRPG on glioma tissues. Results: The SNRPG-mediated inhibitory effect on glioma cells might be due to the targeted prevention of Myc and p53. In addition, the effects of SNRPG loss on p53 levels and cell cycle progression were found to be Myc-dependent. Furthermore, SNRPG was increased in TMZ-resistant GBM cells, and downregulation of SNRPG potentially sensitized resistant cells to TMZ, suggesting that SNRPG deficiency decreases the chemoresistance of GBM cells to TMZ via the p53 signaling pathway.
    [Show full text]
  • RARRES1 Mouse Monoclonal Antibody [Clone ID: OTI1B1] Product Data
    OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TA506084 RARRES1 Mouse Monoclonal Antibody [Clone ID: OTI1B1] Product data: Product Type: Primary Antibodies Clone Name: OTI1B1 Applications: IHC, WB Recommend Dilution: WB 1:4000, IHC 1:150 Reactivity: Human Host: Mouse Isotype: IgG2b Clonality: Monoclonal Immunogen: Full length human recombinant protein of human RARRES1(NP_996846) produced in HEK293T cell. Formulation: PBS (PH 7.3) containing 1% BSA, 50% glycerol and 0.02% sodium azide. Concentration: 1 mg/ml Purification: Purified from mouse ascites fluids or tissue culture supernatant by affinity chromatography (protein A/G) Predicted Protein Size: 33.1 kDa Gene Name: retinoic acid receptor responder 1 Database Link: NP_996846 Entrez Gene 5918 Human Background: This gene was identified as a retinoid acid (RA) receptor-responsive gene. It encodes a type 1 membrane protein. The expression of this gene is upregulated by tazarotene as well as by retinoic acid receptors. The expression of this gene is found to be downregulated in prostate cancer, which is caused by the methylation of its promoter and CpG island. Alternatively spliced transcript variant encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008] Synonyms: LXNL; PERG-1; TIG1 Protein Families: Druggable Genome This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2020 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 3 RARRES1 Mouse Monoclonal Antibody [Clone ID: OTI1B1] – TA506084 Product images: HEK293T cells were transfected with the pCMV6- ENTRY control (Left lane) or pCMV6-ENTRY RARRES1 ([RC205143], Right lane) cDNA for 48 hrs and lysed.
    [Show full text]
  • Cell Atlas of Aqueous Humor Outflow Pathways in Eyes of Humans and Four Model Species Provides Insight Into Glaucoma Pathogenesis
    Cell atlas of aqueous humor outflow pathways in eyes of humans and four model species provides insight into glaucoma pathogenesis Tavé van Zyla,b,c,1,2, Wenjun Yanb,c,1, Alexi McAdamsa,b,c, Yi-Rong Pengb,c,3, Karthik Shekhard,e,4, Aviv Regevd,e,f, Dejan Juricg, and Joshua R. Sanesb,c,2 aDepartment of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear, Boston, MA 02114; bCenter for Brain Science, Harvard University, Cambridge, MA 02138; cDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138; dHoward Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02142; eKoch Institute of Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142; fKlarman Cell Observatory, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142; and gDepartment of Medicine, Harvard Medical School and Massachusetts General Hospital Cancer Center, Boston, MA 02114 Contributed by Joshua R. Sanes, March 10, 2020 (sent for review January 22, 2020; reviewed by Iok-Hou Pang and Joel S. Schuman) Increased intraocular pressure (IOP) represents a major risk factor juxtacanalicular tissue (JCT) prior to being conveyed into a for glaucoma, a prevalent eye disease characterized by death of specialized vessel called Schlemm canal (SC). From SC, AH exits retinal ganglion cells; lowering IOP is the only proven treatment the eye through a network of collector channels (CCs) continu- strategy to delay disease progression. The main determinant of ous with the venous system. The remaining AH exits the anterior IOP is the equilibrium between production and drainage of chamber via the uveoscleral pathway, draining through the in- aqueous humor, with compromised drainage generally viewed terstices of the ciliary muscle (CM) and ultimately exiting the eye as the primary contributor to dangerous IOP elevations.
    [Show full text]
  • Identification of Potential Core Genes in Sevoflurance Induced Myocardial
    Identication of Potential core genes in Sevourance induced Myocardial Energy Metabolism in Patients Undergoing Off-pump Coronary Artery Bypass Graft Surgery using Bioinformatics analysis Hua Lin ( [email protected] ) Tianjin Medical University General Hospital Airport Site Research article Keywords: sevourane, Myocardial Energy Metabolism, Off-pump Coronary Artery Bypass Graft Surgery Posted Date: November 18th, 2019 DOI: https://doi.org/10.21203/rs.2.17434/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/15 Abstract Background: Myocardial ischemia-reperfusion injury always happened after Off-pump coronary artery bypass graft(OPCABG), and this can not be avoided altogether. In this study, we tried to detect potential genes of sevourane-induced myocardial energy metabolism in patients undergoing OPCABG using bioinformatics analysis. Methods: We download and analyze the gene expression prole data from the Gene Expression Omnibus(GEO) database using bioinformatics methods. We downloded the gene expression data from the Gene Expression Omnibus(GEO) database using bioinformatics methods. Gene Ontology(GO) functional annotation analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were used to analysis the screened differentially expressed genes(DEGs). Then, we established a protein–protein interaction (PPI) network to nd hub genes associated with myocardial energy metabolism. Results: Through PPI network, we nd ten hub genes, including JUN, EGR1, ATF3, FOSB, JUNB, DUSP1, EGR2, NR4A1, BTG2, NR4A2. Conclusions: In conclusion, the proteins encoded by EGR1ATF3c-FosBtg2JunBDUSP1NR4A1BTG2 and NR4A2 were related to cardiac function. ATF3, FOSB, JUNB, DUSP1, NR4A1, NR4A2 are related to apoptosis of cardiomyocytes. The protein encoded by BTG2 is related to hypertrophy.
    [Show full text]
  • Systems Genetics in Diversity Outbred Mice Inform BMD GWAS and Identify Determinants of Bone Strength
    ARTICLE https://doi.org/10.1038/s41467-021-23649-0 OPEN Systems genetics in diversity outbred mice inform BMD GWAS and identify determinants of bone strength Basel M. Al-Barghouthi 1,2,8, Larry D. Mesner1,3,8, Gina M. Calabrese1,8, Daniel Brooks4, Steven M. Tommasini 5, Mary L. Bouxsein 4, Mark C. Horowitz5, Clifford J. Rosen 6, Kevin Nguyen1, ✉ Samuel Haddox2, Emily A. Farber1, Suna Onengut-Gumuscu 1,3, Daniel Pomp7 & Charles R. Farber 1,2,3 1234567890():,; Genome-wide association studies (GWASs) for osteoporotic traits have identified over 1000 associations; however, their impact has been limited by the difficulties of causal gene iden- tification and a strict focus on bone mineral density (BMD). Here, we use Diversity Outbred (DO) mice to directly address these limitations by performing a systems genetics analysis of 55 complex skeletal phenotypes. We apply a network approach to cortical bone RNA-seq data to discover 66 genes likely to be causal for human BMD GWAS associations, including the genes SERTAD4 and GLT8D2. We also perform GWAS in the DO for a wide-range of bone traits and identify Qsox1 as a gene influencing cortical bone accrual and bone strength. In this work, we advance our understanding of the genetics of osteoporosis and highlight the ability of the mouse to inform human genetics. 1 Center for Public Health Genomics, School of Medicine, University of Virginia, Charlottesville, VA, USA. 2 Department of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, VA, USA. 3 Department of Public Health Sciences, School of Medicine, University of Virginia, Charlottesville, VA, USA.
    [Show full text]
  • RARRES1 Mouse Monoclonal Antibody [Clone ID: OTI1B3] – TA506088 | Origene
    OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TA506088 RARRES1 Mouse Monoclonal Antibody [Clone ID: OTI1B3] Product data: Product Type: Primary Antibodies Clone Name: OTI1B3 Applications: IF, WB Recommended Dilution: WB 1:200~4000, IF 1:100 Reactivity: Human, Monkey, Mouse, Rat, Dog Host: Mouse Isotype: IgG2b Clonality: Monoclonal Immunogen: Full length human recombinant protein of human RARRES1(NP_996846) produced in HEK293T cell. Formulation: PBS (PH 7.3) containing 1% BSA, 50% glycerol and 0.02% sodium azide. Concentration: 1 mg/ml Purification: Purified from mouse ascites fluids or tissue culture supernatant by affinity chromatography (protein A/G) Conjugation: Unconjugated Storage: Store at -20°C as received. Stability: Stable for 12 months from date of receipt. Predicted Protein Size: 33.1 kDa Gene Name: retinoic acid receptor responder 1 Database Link: NP_996846 Entrez Gene 109222 MouseEntrez Gene 310486 RatEntrez Gene 612298 DogEntrez Gene 703781 MonkeyEntrez Gene 5918 Human P49788 This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 3 RARRES1 Mouse Monoclonal Antibody [Clone ID: OTI1B3] – TA506088 Background: This gene was identified as a retinoid acid (RA) receptor-responsive gene. It encodes a type 1 membrane protein. The expression of this gene is upregulated by tazarotene as well as by retinoic acid receptors. The expression of this gene is found to be downregulated in prostate cancer, which is caused by the methylation of its promoter and CpG island.
    [Show full text]