MicroRNA regulate immunological pathways in T-cells in immune thrombocytopenia (ITP)

被引:52
作者
Jernas, Margareta [1 ]
Nookaew, Intawat [2 ]
Wadenvik, Hans [1 ]
Olsson, Bob [3 ]
机构
[1] Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med, SE-41345 Gothenburg, Sweden
[2] Chalmers Univ Technol, Dept Chem & Biol Engn, S-41296 Gothenburg, Sweden
[3] Univ Gothenburg, Sahlgrenska Acad, Dept Psychiat & Neurochem, SE-41345 Gothenburg, Sweden
基金
瑞典研究理事会;
关键词
MEDIATED CYTOTOXICITY; PURPURA; GENE; IIIA; MECHANISMS; PLATELETS; EPITOPES; PROGRESS;
D O I
10.1182/blood-2012-12-471250
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
MicroRNA are small noncoding RNA molecules that regulate gene expression. To investigate the role of microRNA in immune thrombocytopenia (ITP), we performed genome-wide expression analyses of mRNA and microRNA in T cells from ITP patients and controls. We identified 1915 regulated genes and 22 regulated microRNA that differed between ITP patients and controls. Seventeen of the 22 regulated microRNA were linked to changes in target gene expression; 57 of these target genes were associated with the immune system, eg, T-cell activation and regulation of immunoglobulin production. CXCL13 and IL-21 were two microRNA target genes significantly increased in ITP. We could demonstrate increased plasma levels of CXCL13 and others have reported increased plasma levels of interleukin-21 in ITP. Thus, regulated microRNA were significantly associated with both gene and protein expression of molecules in immunological pathways. We suggest that microRNA may be important regulatory molecules involved in the loss of tolerance in ITP.
引用
收藏
页码:2095 / 2098
页数:4
相关论文
共 29 条
[1]   MECHANISMS OF THROMBOCYTOPENIA IN CHRONIC AUTOIMMUNE THROMBOCYTOPENIC PURPURA - EVIDENCE OF BOTH IMPAIRED PLATELET PRODUCTION AND INCREASED PLATELET CLEARANCE [J].
BALLEM, PJ ;
SEGAL, GM ;
STRATTON, JR ;
GERNSHEIMER, T ;
ADAMSON, JW ;
SLICHTER, SJ .
JOURNAL OF CLINICAL INVESTIGATION, 1987, 80 (01) :33-40
[2]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[3]   A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia [J].
Calin, GA ;
Ferracin, M ;
Cimmino, A ;
Di Leva, G ;
Shimizu, M ;
Wojcik, SE ;
Iorio, MV ;
Visone, R ;
Sever, NI ;
Fabbri, M ;
Iuliano, R ;
Palumbo, T ;
Pichiorri, F ;
Roldo, C ;
Garzon, R ;
Sevignani, C ;
Rassenti, L ;
Alder, H ;
Volinia, S ;
Liu, CG ;
Kipps, TJ ;
Negrini, M ;
Croce, CM .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (17) :1793-1801
[4]   A murine model of severe immune thrombocytopenia is induced by antibody- and CD8+ T cell-mediated responses that are differentially sensitive to therapy [J].
Chow, Leola ;
Aslam, Rukhsana ;
Speck, Edwin R. ;
Kim, Michael ;
Cridland, Norman ;
Webster, Michelle Lee ;
Chen, Pingguo ;
Sahib, Kim ;
Ni, Heyu ;
Lazarus, Alan H. ;
Garvey, M. Bernadette ;
Freedman, John ;
Semple, John W. .
BLOOD, 2010, 115 (06) :1247-1253
[5]   miR-15 and miR-16 induce apoptosis by targeting BCL2 [J].
Cimmino, A ;
Calin, GA ;
Fabbri, M ;
Iorio, MV ;
Ferracin, M ;
Shimizu, M ;
Wojcik, SE ;
Aqeilan, RI ;
Zupo, S ;
Dono, M ;
Rassenti, L ;
Alder, H ;
Volinia, S ;
Liu, CG ;
Kipps, TJ ;
Negrini, M ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (39) :13944-13949
[6]   Medical progress: Immune thrombocytopenic purpura. [J].
Cines, DB ;
Blanchette, VS .
NEW ENGLAND JOURNAL OF MEDICINE, 2002, 346 (13) :995-1008
[7]   Ontology development for biological systems: immunology [J].
Diehl, Alexander D. ;
Lee, Jamie A. ;
Scheuermann, Richard H. ;
Blake, Judith A. .
BIOINFORMATICS, 2007, 23 (07) :913-915
[8]   miRBase: microRNA sequences, targets and gene nomenclature [J].
Griffiths-Jones, Sam ;
Grocock, Russell J. ;
van Dongen, Stijn ;
Bateman, Alex ;
Enright, Anton J. .
NUCLEIC ACIDS RESEARCH, 2006, 34 :D140-D144
[9]   MicroRNA targeting specificity in mammals: Determinants beyond seed pairing [J].
Grimson, Andrew ;
Farh, Kyle Kai-How ;
Johnston, Wendy K. ;
Garrett-Engele, Philip ;
Lim, Lee P. ;
Bartel, David P. .
MOLECULAR CELL, 2007, 27 (01) :91-105
[10]  
HARRINGTON WJ, 1951, J LAB CLIN MED, V38, P1