DOCSLIB.ORG

Gene Expression Profiling Reveals Multiple Protective Influences of The

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Gene Expression Profiling Reveals Multiple Protective Influences of The Gene Expression Profiling Reveals Multiple Protective Influences of the Peptide α -Melanocyte-Stimulating Hormone in Experimental Heart Transplantation This information is current as of September 30, 2021. Gualtiero Colombo, Stefano Gatti, Flavia Turcatti, Andrea Sordi, Luigi R. Fassati, Ferruccio Bonino, James M. Lipton and Anna Catania J Immunol 2005; 175:3391-3401; ; doi: 10.4049/jimmunol.175.5.3391 Downloaded from http://www.jimmunol.org/content/175/5/3391 References This article cites 52 articles, 14 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/175/5/3391.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 30, 2021 • Fast Publication! 4 weeks from acceptance to publication *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 © 2005 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Gene Expression Profiling Reveals Multiple Protective Influences of the Peptide ␣-Melanocyte-Stimulating Hormone in Experimental Heart Transplantation1 †,Luigi R. Fassati ء,Andrea Sordi ء,Stefano Gatti,† Flavia Turcatti ء,Gualtiero Colombo ءFerruccio Bonino,‡ James M. Lipton,§ and Anna Catania2 Novel therapies are sought to increase efficiency and survival of transplanted organs. Previous research on experimental heart transplantation showed that treatment with the anti-inflammatory peptide ␣-melanocyte-stimulating hormone (␣-MSH) prolongs allograft survival. The aim of the present research was to determine the molecular mechanism of this protective activity. Gene expression profile was examined in heart grafts removed on postoperative days 1 and 4 from rats treated with saline or the 4 7 synthetic ␣-MSH analog Nle DPhe (NDP)-␣-MSH. On postoperative day 1, the peptide induced expression of cytoskeleton Downloaded from proteins, intracellular kinases, transcription regulators, metallopeptidases, and protease inhibitors. Conversely, NDP-␣-MSH repressed immune, inflammatory, cell cycle, and protein turnover mediators. Later effects of ␣-MSH treatment included down- regulation of oxidative stress response and up-regulation of ion channels, calcium regulation proteins, phosphatidylinositol sig- naling system, and glycolipidic metabolism. NDP-␣-MSH exerted its effects on both Ag-dependent and -independent injury. The results indicate that NDP-␣-MSH preserves heart function through a broad effect on multiple pathways and suggest that the peptide could improve the outcome of organ transplantation in combination with immunosuppressive treatments. The Journal http://www.jimmunol.org/ of Immunology, 2005, 175: 3391–3401. cute rejection is a significant obstacle to successful or- soon be used clinically as truly novel anti-inflammatory/immuno- gan transplantation and its prevention is crucial for fa- modulatory compounds (4–8). Therefore, we designed research to A vorable clinical outcome. Although immunosuppressive determine the molecular mechanism underlying the protective ef- molecules can reduce rejection, they are associated with serious fects of the peptide. Using complement DNA arrays, an estab- side effects such as organ toxicity, increased viral infection, and lished technique for identification of pathways involved in trans- cancer (1). Because most of these harmful effects are dose-depen- plant rejection and its prevention (9), we found multiple protective dent, reduction of immunosuppressive drug treatment necessary to influences of ␣-MSH in experimental heart transplantation. by guest on September 30, 2021 prevent rejection is a major clinical target. As intragraft inflam- mation is known to promote and accelerate rejection (2), use of Materials and Methods anti-inflammatory compounds that enhance effectiveness of immu- Animals nosuppressive agents could be a successful strategy. Previous research on experimental heart transplantation showed Adult inbred Brown Norway and Lewis male rats (Charles River Labora- ␣ tories) weighing 200–300 g were used in the research. All animals received that treatment with the immunomodulatory peptide -melanocyte- care in compliance with the Principles of Laboratory Animal Care, formu- stimulating hormone (␣-MSH)3 prolongs survival and improves lated by the National Society of Medical Research, and the Guide for the allograft histopathology (3). Such beneficial effects were associ- Care and Use of Laboratory Animals, prepared by the National Academy ated with reduced intragraft expression of cytokines, chemokines, of Sciences and published by the National Institutes of Health (National Institutes of Health Publication No. 86–23). and adhesion molecules (3). ␣-MSH or its synthetic analogues may Surgical procedures Rats were anesthetized with a combination of 100 mg/kg ketamine and 6 *Division of Internal Medicine, †Division of Liver Transplantation, and ‡Scientific Direction, Fondazione Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS) mg/kg xylazine injected i.p. During anesthesia, heart rate, ventilation rate, Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano, Italy; and §Zen- and temperature were closely monitored. Brown Norway donor hearts were gen, Woodland Hills, CA 91367 transplanted into either the MHC incompatible Lewis rats (allografts) or into Brown Norway rats (isografts). The donor heart was transplanted het- Received for publication May 17, 2005. Accepted for publication June 24, 2005. erotopically into the abdominal cavity of the recipient using the technique The costs of publication of this article were defrayed in part by the payment of page described by Ono and Lindsey (10). All cardiac transplants had good initial charges. This article must therefore be hereby marked advertisement in accordance contractile function. Graft function was monitored by palpation through the with 18 U.S.C. Section 1734 solely to indicate this fact. abdominal wall twice daily. There were no early deaths nor graft rejections 1 This work was supported by Progetto di Ricerca “Meccanismi molecolari del danno during the study period. At each planned interval, rats were euthanized nel trapianto singenico e nell’allotrapianto”, Ospedale Maggiore di Milano, Italy, and with thoracotomy under ketamine and xylazine anesthesia. The abdomen Progetto di Ricerca Finalizzata “Strategie innovative per il trapianto di fegato was incised and the heart grafts were immediately removed. (SITF)”, Ministero della Salute, Italy. 2 Address correspondence and reprint requests to Dr. Anna Catania, Divisione di Treatments Medicina Interna, Pad. Granelli, Ospedale Maggiore Policlinico, Via F. Sforza 35, Milano 20122, Italy. E-mail address: [email protected] Each treatment group included five rats. Allograft recipients assigned to 4 7 3 ␣ ␣ active treatment received i.p. injections of 100 ␮gofNleDPhe (NPD)- Abbreviations used in this paper: -MSH, -melanocyte stimulating hormone; ␣ NDP, Nle4DPhe7; POD, postoperative day; SAM, significance analysis of microar- -MSH (11) (kindly provided by Prof. P. Grieco, University of Naples, rays; FDR, false discovery rate; CT, cycle threshold; PKC, protein kinase C; Plc, Naples, Italy) dissolved in 0.5 ml of saline, every 12 h. Treatment was phospholipase C; Adcy6, adenylyl cyclase VI. started 1 h before transplantation and continued until sacrifice. Untreated Copyright © 2005 by The American Association of Immunologists, Inc. 0022-1767/05/$02.00 3392 EFFECT OF ␣-MSH ON GRAFT TRANSCRIPTIONAL PROFILE FIGURE 1. Histology of cardiac grafts. H&E staining (ϫ120) of a control nontransplanted heart (A); POD4 cardiac allograft from a saline-treated rat (B) and from an NDP-␣-MSH-treated animal (C). allograft recipients and isograft recipients received i.p. parallel injections sen samples for each allograft group and obtained consistent results (data of 0.5 ml of saline. not shown). Cardiac isografts were used to estimate heart injury caused by surgical procedures alone and were harvested on postoperative day (POD) 1. Al- Analysis of macroarray data Downloaded from lografts were harvested on POD 1 or 4. Two Brown Norway donor hearts Normalization. Phosphorimager scans were analyzed using AtlasImage were subjected to cold ischemia of similar duration and not transplanted. software (version 2.7; BD Biosciences/Clontech). A given gene was con- They served as nontransplanted controls. Heart grafts were sectioned coro- sidered to be detectable if its intensity was at least twice the global external nally. Two sections were snap-frozen in liquid nitrogen and stored at background of the array. The background level was subtracted from the Ϫ 80°C for RNA extraction. One section was fixed in 10% buffered for- intensity of each spot to generate the raw data for each gene. Raw data were malin and paraffin-embedded for light microscopy examination. normalized according to the sum of the intensities global normalization method. The normalization coefficient was obtained by dividing the global
Load more

Recommended publications
  • KLF2 Induced
    UvA-DARE (Digital Academic Repository) The transcription factor KLF2 in vascular biology Boon, R.A. Publication date 2008 Link to publication Citation for published version (APA): Boon, R. A. (2008). The transcription factor KLF2 in vascular biology. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:23 Sep 2021 Supplementary data: Genes induced by KLF2 Dekker et al. LocusLink Accession Gene Sequence Description Fold p-value ID number symbol change (FDR) 6654 AK022099 SOS1 cDNA FLJ12037 fis, clone HEMBB1001921. 100.00 5.9E-09 56999 AF086069 ADAMTS9 full length insert cDNA clone YZ35C05. 100.00 1.2E-09 6672 AF085934 SP100 full length insert cDNA clone YR57D07. 100.00 6.7E-13 9031 AF132602 BAZ1B Williams Syndrome critical region WS25 mRNA, partial sequence.
    [Show full text]
  • Gentaur Products List
    Chapter 2 : Gentaur Products List • Rabbit Anti LAMR1 Polyclonal Antibody Cy5 Conjugated Conjugated • Rabbit Anti Podoplanin gp36 Polyclonal Antibody Cy5 • Rabbit Anti LAMR1 CT Polyclonal Antibody Cy5 • Rabbit Anti phospho NFKB p65 Ser536 Polyclonal Conjugated Conjugated Antibody Cy5 Conjugated • Rabbit Anti CHRNA7 Polyclonal Antibody Cy5 Conjugated • Rat Anti IAA Monoclonal Antibody Cy5 Conjugated • Rabbit Anti EV71 VP1 CT Polyclonal Antibody Cy5 • Rabbit Anti Connexin 40 Polyclonal Antibody Cy5 • Rabbit Anti IAA Indole 3 Acetic Acid Polyclonal Antibody Conjugated Conjugated Cy5 Conjugated • Rabbit Anti LHR CGR Polyclonal Antibody Cy5 Conjugated • Rabbit Anti Integrin beta 7 Polyclonal Antibody Cy5 • Rabbit Anti Natrexone Polyclonal Antibody Cy5 Conjugated • Rabbit Anti MMP 20 Polyclonal Antibody Cy5 Conjugated Conjugated • Rabbit Anti Melamine Polyclonal Antibody Cy5 Conjugated • Rabbit Anti BCHE NT Polyclonal Antibody Cy5 Conjugated • Rabbit Anti NAP1 NAP1L1 Polyclonal Antibody Cy5 • Rabbit Anti Acetyl p53 K382 Polyclonal Antibody Cy5 • Rabbit Anti BCHE CT Polyclonal Antibody Cy5 Conjugated Conjugated Conjugated • Rabbit Anti HPV16 E6 Polyclonal Antibody Cy5 Conjugated • Rabbit Anti CCP Polyclonal Antibody Cy5 Conjugated • Rabbit Anti JAK2 Polyclonal Antibody Cy5 Conjugated • Rabbit Anti HPV18 E6 Polyclonal Antibody Cy5 Conjugated • Rabbit Anti HDC Polyclonal Antibody Cy5 Conjugated • Rabbit Anti Microsporidia protien Polyclonal Antibody Cy5 • Rabbit Anti HPV16 E7 Polyclonal Antibody Cy5 Conjugated • Rabbit Anti Neurocan Polyclonal
    [Show full text]
  • ONLINE SUPPLEMENTARY TABLE Table 2. Differentially Expressed
    ONLINE SUPPLEMENTARY TABLE Table 2. Differentially Expressed Probe Sets in Livers of GK Rats. A. Immune/Inflammatory (67 probe sets, 63 genes) Age Strain Probe ID Gene Name Symbol Accession Gene Function 5 WKY 1398390_at small inducible cytokine B13 precursor Cxcl13 AA892854 chemokine activity; lymph node development 5 WKY 1389581_at interleukin 33 Il33 BF390510 cytokine activity 5 WKY *1373970_at interleukin 33 Il33 AI716248 cytokine activity 5 WKY 1369171_at macrophage stimulating 1 (hepatocyte growth factor-like) Mst1; E2F2 NM_024352 serine-throenine kinase; tumor suppression 5 WKY 1388071_x_at major histocompatability antigen Mhc M24024 antigen processing and presentation 5 WKY 1385465_at sialic acid binding Ig-like lectin 5 Siglec5 BG379188 sialic acid-recognizing receptor 5 WKY 1393108_at major histocompatability antigen Mhc BM387813 antigen processing and presentation 5 WKY 1388202_at major histocompatability antigen Mhc BI395698 antigen processing and presentation 5 WKY 1371171_at major histocompatability antigen Mhc M10094 antigen processing and presentation 5 WKY 1370382_at major histocompatability antigen Mhc BI279526 antigen processing and presentation 5 WKY 1371033_at major histocompatability antigen Mhc AI715202 antigen processing and presentation 5 WKY 1383991_at leucine rich repeat containing 8 family, member E Lrrc8e BE096426 proliferation and activation of lymphocytes and monocytes. 5 WKY 1383046_at complement component factor H Cfh; Fh AA957258 regulation of complement cascade 4 WKY 1369522_a_at CD244 natural killer
    [Show full text]
  • CDH12 Cadherin 12, Type 2 N-Cadherin 2 RPL5 Ribosomal
    5 6 6 5 . 4 2 1 1 1 2 4 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 2 A A A A A A A A A A A A A A A A A A A A C C C C C C C C C C C C C C C C C C C C R R R R R R R R R R R R R R R R R R R R B , B B B B B B B B B B B B B B B B B B B , 9 , , , , 4 , , 3 0 , , , , , , , , 6 2 , , 5 , 0 8 6 4 , 7 5 7 0 2 8 9 1 3 3 3 1 1 7 5 0 4 1 4 0 7 1 0 2 0 6 7 8 0 2 5 7 8 0 3 8 5 4 9 0 1 0 8 8 3 5 6 7 4 7 9 5 2 1 1 8 2 2 1 7 9 6 2 1 7 1 1 0 4 5 3 5 8 9 1 0 0 4 2 5 0 8 1 4 1 6 9 0 0 6 3 6 9 1 0 9 0 3 8 1 3 5 6 3 6 0 4 2 6 1 0 1 2 1 9 9 7 9 5 7 1 5 8 9 8 8 2 1 9 9 1 1 1 9 6 9 8 9 7 8 4 5 8 8 6 4 8 1 1 2 8 6 2 7 9 8 3 5 4 3 2 1 7 9 5 3 1 3 2 1 2 9 5 1 1 1 1 1 1 5 9 5 3 2 6 3 4 1 3 1 1 4 1 4 1 7 1 3 4 3 2 7 6 4 2 7 2 1 2 1 5 1 6 3 5 6 1 3 6 4 7 1 6 5 1 1 4 1 6 1 7 6 4 7 e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m
    [Show full text]
  • HOXB6 Homeo Box B6 HOXB5 Homeo Box B5 WNT5A Wingless-Type
    5 6 6 5 . 4 2 1 1 1 2 4 6 4 3 2 9 9 7 0 5 7 5 8 6 4 0 8 2 3 1 8 3 7 1 0 0 4 0 2 5 0 8 7 5 4 1 1 0 3 6 0 4 8 3 7 4 7 6 9 6 7 1 5 0 8 1 4 1 1 7 1 0 0 4 2 0 8 1 1 1 2 5 3 5 0 7 2 6 9 1 2 1 8 3 5 2 9 8 0 6 0 9 5 1 9 9 2 1 1 6 0 2 3 0 3 6 9 1 6 5 5 7 1 1 2 1 1 7 5 4 6 6 4 1 1 2 8 4 7 1 6 2 7 7 5 4 3 2 4 3 6 9 4 1 7 1 3 4 1 2 1 3 1 1 4 7 3 1 1 1 1 5 3 2 6 1 5 1 3 5 4 5 2 3 1 1 6 1 7 3 2 5 4 3 1 6 1 5 3 1 7 6 5 1 1 1 4 6 1 6 2 7 2 1 2 e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S HOXB6 homeo box B6 HOXB5 homeo box B5 WNT5A wingless-type MMTV integration site family, member 5A WNT5A wingless-type MMTV integration site family, member 5A FKBP11 FK506 binding protein 11, 19 kDa EPOR erythropoietin receptor SLC5A6 solute carrier family 5 sodium-dependent vitamin transporter, member 6 SLC5A6 solute carrier family 5 sodium-dependent vitamin transporter, member 6 RAD52 RAD52 homolog S.
    [Show full text]
  • Antigen-Specific Memory CD4 T Cells Coordinated Changes in DNA
    Downloaded from http://www.jimmunol.org/ by guest on September 24, 2021 is online at: average * The Journal of Immunology The Journal of Immunology published online 18 March 2013 from submission to initial decision 4 weeks from acceptance to publication http://www.jimmunol.org/content/early/2013/03/17/jimmun ol.1202267 Coordinated Changes in DNA Methylation in Antigen-Specific Memory CD4 T Cells Shin-ichi Hashimoto, Katsumi Ogoshi, Atsushi Sasaki, Jun Abe, Wei Qu, Yoichiro Nakatani, Budrul Ahsan, Kenshiro Oshima, Francis H. W. Shand, Akio Ametani, Yutaka Suzuki, Shuichi Kaneko, Takashi Wada, Masahira Hattori, Sumio Sugano, Shinichi Morishita and Kouji Matsushima J Immunol Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Author Choice option Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Freely available online through http://www.jimmunol.org/content/suppl/2013/03/18/jimmunol.120226 7.DC1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material Permissions Email Alerts Subscription Author Choice Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2013 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 24, 2021. Published March 18, 2013, doi:10.4049/jimmunol.1202267 The Journal of Immunology Coordinated Changes in DNA Methylation in Antigen-Specific Memory CD4 T Cells Shin-ichi Hashimoto,*,†,‡ Katsumi Ogoshi,* Atsushi Sasaki,† Jun Abe,* Wei Qu,† Yoichiro Nakatani,† Budrul Ahsan,x Kenshiro Oshima,† Francis H.
    [Show full text]
  • Strand Breaks for P53 Exon 6 and 8 Among Different Time Course of Folate Depletion Or Repletion in the Rectosigmoid Mucosa
    SUPPLEMENTAL FIGURE COLON p53 EXONIC STRAND BREAKS DURING FOLATE DEPLETION-REPLETION INTERVENTION Supplemental Figure Legend Strand breaks for p53 exon 6 and 8 among different time course of folate depletion or repletion in the rectosigmoid mucosa. The input of DNA was controlled by GAPDH. The data is shown as ΔCt after normalized to GAPDH. The higher ΔCt the more strand breaks. The P value is shown in the figure. SUPPLEMENT S1 Genes that were significantly UPREGULATED after folate intervention (by unadjusted paired t-test), list is sorted by P value Gene Symbol Nucleotide P VALUE Description OLFM4 NM_006418 0.0000 Homo sapiens differentially expressed in hematopoietic lineages (GW112) mRNA. FMR1NB NM_152578 0.0000 Homo sapiens hypothetical protein FLJ25736 (FLJ25736) mRNA. IFI6 NM_002038 0.0001 Homo sapiens interferon alpha-inducible protein (clone IFI-6-16) (G1P3) transcript variant 1 mRNA. Homo sapiens UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 15 GALNTL5 NM_145292 0.0001 (GALNT15) mRNA. STIM2 NM_020860 0.0001 Homo sapiens stromal interaction molecule 2 (STIM2) mRNA. ZNF645 NM_152577 0.0002 Homo sapiens hypothetical protein FLJ25735 (FLJ25735) mRNA. ATP12A NM_001676 0.0002 Homo sapiens ATPase H+/K+ transporting nongastric alpha polypeptide (ATP12A) mRNA. U1SNRNPBP NM_007020 0.0003 Homo sapiens U1-snRNP binding protein homolog (U1SNRNPBP) transcript variant 1 mRNA. RNF125 NM_017831 0.0004 Homo sapiens ring finger protein 125 (RNF125) mRNA. FMNL1 NM_005892 0.0004 Homo sapiens formin-like (FMNL) mRNA. ISG15 NM_005101 0.0005 Homo sapiens interferon alpha-inducible protein (clone IFI-15K) (G1P2) mRNA. SLC6A14 NM_007231 0.0005 Homo sapiens solute carrier family 6 (neurotransmitter transporter) member 14 (SLC6A14) mRNA.
    [Show full text]
  • Supplemental Table 1 List of Genes Differentially Expressed In
    Supplemental Table 1 List of genes differentially expressed in normal nasopharyngeal epithelium (N), metaplastic and displastic lesions (R), and carcinoma (T). Parametric Permutation Geom Geom Geom Unique Description Clone UG Gene symbol Map p-value p-value mean mean mean id cluster of of of ratios ratios ratios in in in class class class 1 : N 2 : R 3 : T 1 p < 1e-07 0 0.061 0.123 2.708 169329 secretory leukocyte protease IncytePD:2510171 Hs.251754 SLPI 20q12 inhibitor (antileukoproteinase) 2 p < 1e-07 0 0.125 0.394 1.863 163628 sodium channel, nonvoltage-gated IncytePD:1453049 Hs.446415 SCNN1A 12p13 1 alpha 3 p < 1e-07 0 0.122 0.046 1.497 160401 carcinoembryonic antigen-related IncytePD:2060355 Hs.73848 CEACAM6 19q13.2 cell adhesion molecule 6 (non- specific cross reacting antigen) 4 p < 1e-07 0 0.675 1.64 5.594 165101 monoglyceride lipase IncytePD:2174920 Hs.6721 MGLL 3q21.3 5 p < 1e-07 0 0.182 0.487 0.998 166827 nei endonuclease VIII-like 1 (E. IncytePD:1926409 Hs.28355 NEIL1 15q22.33 coli) 6 p < 1e-07 0 0.194 0.339 0.915 162931 hypothetical protein FLJ22418 IncytePD:2816379 Hs.36563 FLJ22418 1p11.1 7 p < 1e-07 0 1.313 0.645 13.593 162399 S100 calcium binding protein P IncytePD:2060823 Hs.2962 S100P 4p16 8 p < 1e-07 0 0.157 1.445 2.563 169315 selenium binding protein 1 IncytePD:2591494 Hs.334841 SELENBP1 1q21-q22 9 p < 1e-07 0 0.046 0.738 1.213 160115 prominin-like 1 (mouse) IncytePD:2070568 Hs.112360 PROML1 4p15.33 10 p < 1e-07 0 0.787 2.264 3.013 167294 HRAS-like suppressor 3 IncytePD:1969263 Hs.37189 HRASLS3 11q12.3 11 p < 1e-07 0 0.292 0.539 1.493 168221 Homo sapiens cDNA FLJ13510 IncytePD:64451 Hs.37896 2 fis, clone PLACE1005146.
    [Show full text]
  • Supplemental Figure 1 Characterization of Lung Tumors In
    Supplemental Figure 1 Characterization of lung tumors in KC mice. (A) Scatter plots of visible spontaneous tumors counted on the lung surfaces at necropsy. Each dot represents a value from a single mouse, and the bars and whiskers show the mean SD for each cohort from a single experiment. P value, two-tailed Student’s t-test. (B) Histologic analysis of spontaneous lung tumors in (A). Results indicate the numbers of lung lesions per histologic subtype per genotype. N, cohort sample sizes. P values, Fisher's exact test. Supplemental Figure 2 Surfactant protein C (SPC) expression in p21-deficient (KC) and –replete (K) tumor cell lines. Immunofluorescence staining with anti-surfactant protein C antibody (green) or normal IgG as a negative control. DAPI, blue. SPC/DAPI and IgG/DAPI are merged images. Scale bar, 20 µm. Supplemental Figure 3 Somatic recombination of latent KrasG12D allele and detection of p21 protein in p21-deficient (KC) and –replete (K) tumor cell lines. (A) PCR analysis of the K-rasLA1 and K-rasWT alleles in genomic DNA. Somatic recombination of the K-rasLA1 allele leads to loss of the PCR product (upper band, arrow). Wild-type K-ras allele detected (250 bp). Tail DNAs from KrasLA1 mice (KrasLA1/+) and wild-type mice (Kras+/+) were used as positive and negative controls, respectively, for the presence of the germline K-rasLA1 allele. (B) Immunoblot analysis of p21 expression. Actin was used as a loading control. Supplemental Figure 4 Growth and metastasis of p21-deficient (KC) tumor cell lines in Cdkn1a-null or –wild-type mice.
    [Show full text]
  • Adpla Ablation Increases Lipolysis and Prevents Obesity Induced by High-Fat Feeding Or Leptin Deficiency
    ARTICLES AdPLA ablation increases lipolysis and prevents obesity induced by high-fat feeding or leptin deficiency Kathy Jaworski1,4, Maryam Ahmadian1,4, Robin E Duncan1,4, Eszter Sarkadi-Nagy1, Krista A Varady1, Marc K Hellerstein1, Hui-Young Lee2, Varman T Samuel2, Gerald I Shulman2, Kee-Hong Kim3, Sarah de Val1, Chulho Kang3 & Hei Sook Sul1 A main function of white adipose tissue is to release fatty acids from stored triacylglycerol for other tissues to use as an energy source. Whereas endocrine regulation of lipolysis has been extensively studied, autocrine and paracrine regulation is not well understood. Here we describe the role of the newly identified major adipocyte phospholipase A2, AdPLA (encoded by Pla2g16, also called HREV107), in the regulation of lipolysis and adiposity. AdPLA-null mice have a markedly higher rate of lipolysis owing to increased cyclic AMP levels arising from the marked reduction in the amount of adipose prostaglandin E2 that binds the Gai-coupled receptor, EP3. AdPLA-null mice have markedly reduced adipose tissue mass and triglyceride content but normal adipogenesis. They also have higher energy expenditure with increased fatty acid oxidation within adipocytes. AdPLA-deficient ob/ob mice remain hyperphagic but lean, with increased energy expenditure, yet have ectopic triglyceride storage and insulin resistance. AdPLA is a major regulator of adipocyte lipolysis and is crucial for the development of obesity. 8 Triacylglycerol in adipose tissue is the major energy storage form hydrolysis of the sn-2 ester bond of phospholipids . The PLA2 in mammals. An imbalance between energy intake and expenditure enzymes function in remodeling of membrane phospholipids by can result in excess triacylglycerol accumulation in this tissue, acylation and deacylation cycles8.
    [Show full text]
  • (12) STANDARD PATENT (11) Application No. AU 2006202209 B2 (19) AUSTRALIAN PATENT OFFICE
    (12) STANDARD PATENT (11) Application No. AU 2006202209 B2 (19) AUSTRALIAN PATENT OFFICE (54) Title Amniotic fluid derived cells (51) International Patent Classification(s) C12N 5/02 (2006.01) A61P 1/18 (2006.01) A61K 35/50 (2006.01) A61P 5/50 (2006.01) A61K 48/00 (2006.01) C12N 5/073 (2010.01) (21) Application No: 2006202209 (22) Date of Filing: 2006.05.25 (30) Priority Data (31) Number (32) Date (33) Country 60/743,821 2006.03.27 US 60/685,607 2005.05.27 us (43) Publication Date: 2006.12.14 (43) Publication Journal Date: 2006.12.14 (44) Accepted Journal Date: 2011.04.14 (71) Applicant(s) Lifescan, Inc. (72) Inventor(s) Xu, Jean;Rezania, Alireza (74) Agent / Attorney Callinans, 1193 Toorak Road, Camberwell, VIC, 3124 (56) Related Art Fauza et al (2004) Best Practice & Research Clinical Obstetrics and Gynaecology, vol. 18, pps 877-891 Tsai et al (2004) Human Reproduction vol. 19, pps 1450-1456 W02005/017117 A2 Wei et al (2003) Cell Transplantation vol. 12, pps. 545-552 Held et al (1984) Prenatal Diagnosis vol. 4, pps 171-179 in 't Anker et al (2003) Blood vol. 102, pps 1548-1549 ABSTRACT This invention relates to an expandable population of amniotic fluid-derived cells that can be differentiated into a p-cell lineage. This invention also provides methods for isolating and expanding such amniotic fluid-derived cells, as well as related 5 methods and compositions for utilizing such cells in the therapeutic treatment of diabetes. 24/05/06,15735 specigp,2 P/00/0II Regulation 3.2 AUSTRALIA Patents Act 1990 COMPLETE SPECIFICATION FOR A STANDARD PATENT ORIGINAL TO BE COMPLETED BY APPLICANT Name of Applicant: LIFESCAN, INC.
    [Show full text]
  • Flavone Effects on the Proteome and Transcriptome of Colonocytes in Vitro and in Vivo and Its Relevance for Cancer Prevention and Therapy
    TECHNISCHE UNIVERSITÄT MÜNCHEN Lehrstuhl für Ernährungsphysiologie Flavone effects on the proteome and transcriptome of colonocytes in vitro and in vivo and its relevance for cancer prevention and therapy Isabel Winkelmann Vollständiger Abdruck der von der Fakultät Wissenschaftszentrum Weihenstephan für Ernährung, Landnutzung und Umwelt der Technischen Universität München zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften genehmigten Dissertation. Vorsitzender: Univ.-Prof. Dr. D. Haller Prüfer der Dissertation: 1. Univ.-Prof. Dr. H. Daniel 2. Univ.-Prof. Dr. U. Wenzel (Justus-Liebig-Universität Giessen) 3. Prof. Dr. E.C.M. Mariman (Maastricht University, Niederlande) schriftliche Beurteilung Die Dissertation wurde am 24.08.2009 bei der Technischen Universität München eingereicht und durch die Fakultät Wissenschaftszentrum Weihenstephan für Ernährung, Landnutzung und Umwelt am 25.11.2009 angenommen. Die Forschung ist immer auf dem Wege, nie am Ziel. (Adolf Pichler) Table of contents 1. Introduction .......................................................................................................... 1 1.1. Cancer and carcinogenesis .................................................................................. 2 1.2. Colorectal Cancer ............................................................................................... 3 1.2.1. Hereditary forms of CRC ........................................................................................ 4 1.2.2. Sporadic forms of CRC ..........................................................................................
    [Show full text]