Download PDF
Thromb Haemost 2013; 110(06): 1207-1214
DOI: 10.1160/TH13-07-0623
Platelets and Blood Cells
Schattauer GmbH

MiR-223 is dispensable for platelet production and function in mice

Simon Leierseder
1   Institut für Pharmakologie und Toxikologie, Technische Universität München, Munich, Germany
,
Tobias Petzold   *
2   Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität, Munich, Germany
,
Lin Zhang   *
2   Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität, Munich, Germany
3   Current affiliations: Heart Failure Institute, Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China
4   Current affiliation: Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China
,
Xavier Loyer
1   Institut für Pharmakologie und Toxikologie, Technische Universität München, Munich, Germany
5   Current affiliation: Inserm U970, Paris Cardiovascular Research Center, Paris, France
,
Steffen Massberg
2   Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität, Munich, Germany
6   DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
,
Stefan Engelhardt
1   Institut für Pharmakologie und Toxikologie, Technische Universität München, Munich, Germany
6   DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
› Author Affiliations Financial support: This work was supported in part by grants from the Fondation Leducq and the Bavarian Ministry of Sciences, Research and the Arts in the framework of the Bavarian Molecular Biosystems Research Network (to S.E.) and the DFG (SFB914) and the FP7 EU project PRESTIGE (to S.M.).
Further Information

Publication History

Received: 29 July 2013

Accepted after major revision: 14 September 2013

Publication Date:
30 November 2017 (online)

Also available at
    Permissions and Reprints

Referred to by:

miR-223: sailing to terra incognita for microRNAs in plateletsThromb Haemost 2013; 110(12): 1112-1113
DOI: 10.1160/TH13-10-0882

Summary

MicroRNAs (miRNAs) are key physiological regulators in multiple cell types. Here, we assessed platelet production and function in mice deficient in miR-223, one of the most abundantly expressed miRNAs in platelets and megakaryocytes. We found platelet number, size, lifespan as well as surface expression of platelet adhesion receptors to be unchanged in miR-223-deficient mice. Likewise, loss of miR-223 did not affect platelet activation, adhesion and aggregation and also had no effect on bleeding times. Moreover, miR-223 null megakaryocytes developed normally and were capable to form pro-platelets. However, we detected a transient delay in the recovery of platelet numbers following antibody-induced platelet depletion in miR-223-deficient animals. This delay was not observed after transplantation of bone marrow from miR-223-deficient animals into wild-type recipients, indicating a non-cell-autonomous role of miR-223 for thrombopoiesis. Overall, our data indicate a surprisingly modest role of miR-223 in platelet production, while the function of platelets does not seem to depend on miR-223.

Keywords

MicroRNA - platelets - megakaryocytes - transgenic mice

* These authors contributed equally.


 

  • References

  • 1 Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell 2009; 136: 215-233.
    CrossrefPubMedGoogle Scholar
  • 2 Bonauer A, Carmona G, Iwasaki M. et al. MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science 2009; 324: 1710-1713.
    CrossrefPubMedGoogle Scholar
  • 3 Van Rooij E, Sutherland LB, Qi X. et al. Control of stress-dependent cardiac growth and gene expression by a microRNA. Science 2007; 316: 575-579.
    CrossrefPubMedGoogle Scholar
  • 4 Ganesan J, Ramanujam D, Sassi Y. et al. MiR-378 Controls Cardiac Hypertrophy by Combined Repression of Mitogen-Activated Protein Kinase Pathway Factors. Circulation 2013; 127: 2097-2106.
    CrossrefPubMedGoogle Scholar
  • 5 Thum T, Gross C, Fiedler J. et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature 2008; 456: 980-984.
    CrossrefPubMedGoogle Scholar
  • 6 Chen C-Z, Li L, Lodish HF. et al. MicroRNAs modulate hematopoietic lineage differentiation. Science 2004; 303: 83-86.
    CrossrefPubMedGoogle Scholar
  • 7 Zernecke A, Bidzhekov K, Noels H. et al. Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci Signal 2009; 2: ra81.
    CrossrefPubMedGoogle Scholar
  • 8 Lu J, Guo S, Ebert BL. et al. MicroRNA-mediated control of cell fate in megakaryocyte-erythrocyte progenitors. Dev Cell 2008; 14: 843-853.
    CrossrefPubMedGoogle Scholar
  • 9 Navarro F, Gutman D, Meire E. et al. miR-34a contributes to megakaryocytic differentiation of K562 cells independently of p53. Blood 2009; 114: 2181-2192.
    CrossrefPubMedGoogle Scholar
  • 10 Starczynowski DT, Kuchenbauer F, Argiropoulos B. et al. Identification of miR-145 and miR-146a as mediators of the 5q-syndrome phenotype. Nat Med 2010; 16: 49-58.
    CrossrefPubMedGoogle Scholar
  • 11 Weyrich AS, Schwertz H, Kraiss LW. et al. Protein synthesis by platelets: historical and new perspectives. J Thromb Haemost 2009; 7: 241-246.
    CrossrefPubMedGoogle Scholar
  • 12 Landry P, Plante I, Ouellet DL. et al. Existence of a microRNA pathway in anucleate platelets. Nat Struct Mol Biol 2009; 16: 961-966.
    CrossrefPubMedGoogle Scholar
  • 13 Kondkar AA, Bray MS, Leal SM. et al. VAMP8/endobrevin is overexpressed in hyperreactive human platelets: suggested role for platelet microRNA. J Thromb Haemost 2010; 8: 369-378.
    CrossrefPubMedGoogle Scholar
  • 14 Nagalla S, Shaw C, Kong X. et al. Platelet microRNA-mRNA coexpression profiles correlate with platelet reactivity. Blood 2011; 117: 5189-5197.
    CrossrefPubMedGoogle Scholar
  • 15 Hussein K, Theophile K, Dralle W. et al. MicroRNA expression profiling of megakaryocytes in primary myelofibrosis and essential thrombocythemia. Platelets 2009; 20: 391-400.
    CrossrefPubMedGoogle Scholar
  • 16 Petriv OI, Kuchenbauer F, Delaney AD. et al. Comprehensive microRNA expression profiling of the hematopoietic hierarchy. Proc Natl Acad Sci USA 2010; 107: 15443-15448.
    CrossrefPubMedGoogle Scholar
  • 17 Willeit P, Zampetaki A, Dudek K. et al. Circulating MicroRNAs as Novel Biomarkers for Platelet Activation. Circ Res 2013; 112: 595-600.
    CrossrefPubMedGoogle Scholar
  • 18 Wang K, Yuan Y, Cho J-H. et al. Comparing the MicroRNA spectrum between serum and plasma. PloS One 2012; 7: e41561.
    CrossrefPubMedGoogle Scholar
  • 19 Plé H, Landry P, Benham A. et al. The repertoire and features of human platelet microRNAs. PloS One 2012; 7: e50746.
    CrossrefPubMedGoogle Scholar
  • 20 Hunter MP, Ismail N, Zhang X. et al. Detection of microRNA expression in human peripheral blood microvesicles. PloS One 2008; 3: e3694.
    CrossrefPubMedGoogle Scholar
  • 21 Osman A, Fälker K. Characterization of human platelet microRNA by quantitative PCR coupled with an annotation network for predicted target genes. Platelets 2011; 22: 433-441.
    CrossrefPubMedGoogle Scholar
  • 22 Zampetaki A, Willeit P, Tilling L. et al. Prospective study on circulating MicroRNAs and risk of myocardial infarction. J Am Coll Cardiol 2012; 60: 290-299.
    CrossrefPubMedGoogle Scholar
  • 23 Bray PF, McKenzie SE, Edelstein LC. et al. The complex transcriptional landscape of the anucleate human platelet. BMC Genomics 2013; 14: 1.
    CrossrefPubMedGoogle Scholar
  • 24 Xu X, Gnatenko D V, Ju J. et al. Systematic analysis of microRNA fingerprints in thrombocythemic platelets using integrated platforms. Blood 2012; 120: 3575-3585.
    CrossrefPubMedGoogle Scholar
  • 25 Zhuang G, Meng C, Guo X. et al. A Novel Regulator of Macrophage Activation: miR-223 in Obesity-Associated Adipose Tissue Inflammation. Circulation 2012; 125: 2892-2903.
    CrossrefPubMedGoogle Scholar
  • 26 Johnnidis JB, Harris MH, Wheeler RT. et al. Regulation of progenitor cell proliferation and granulocyte function by microRNA-223. Nature 2008; 451: 1125-1129.
    CrossrefPubMedGoogle Scholar
  • 27 Robinson M, MacHin S, Mackie I. et al. In vivo biotinylation studies: specificity of labelling of reticulated platelets by thiazole orange and mepacrine. Br J Haematol 2000; 108: 859-864.
    CrossrefPubMedGoogle Scholar
  • 28 Mazharian A, Thomas SG, Dhanjal TS. et al. Critical role of Src-Syk-PLCγ2 signaling in megakaryocyte migration and thrombopoiesis. Blood 2010; 116: 793-800.
    CrossrefPubMedGoogle Scholar
  • 29 Gatsiou A, Boeckel J-N, Randriamboavonjy V. et al. MicroRNAs in platelet biogenesis and function: implications in vascular homeostasis and inflammation. Curr Vasc Pharmacol 2012; 10: 524-531.
    CrossrefPubMedGoogle Scholar
  • 30 Bluteau D, Lordier L, Di Stefano A. et al. Regulation of megakaryocyte maturation and platelet formation. J Thromb Haemost 2009; 7 (Suppl. 01) 227-234.
    CrossrefPubMedGoogle Scholar
  • 31 Felli N, Pedini F, Romania P. et al. MicroRNA 223-dependent expression of LMO2 regulates normal erythropoiesis. Haematologica 2009; 94: 479-486.
    CrossrefPubMedGoogle Scholar
  • 32 Yuan J-Y, Wang F, Yu J. et al. MicroRNA-223 reversibly regulates erythroid and megakaryocytic differentiation of K562 cells. J Cell Mol Med 2009; 13: 4551-4559.
    CrossrefPubMedGoogle Scholar
  • 33 Shi R, Ge L, Zhou X. et al. Decreased platelet miR-223 expression is associated with high on-clopidogrel platelet reactivity. Thromb Res 2013; 1-6.
    PubMedGoogle Scholar
  • 34 Zampetaki A, Kiechl S, Drozdov I. et al. Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res 2010; 107: 810-817.
    CrossrefPubMedGoogle Scholar
  • 35 Engelhardt S. Small RNA biomarkers come of age. J Am Coll Cardiol 2012; 60: 300-303.
    CrossrefPubMedGoogle Scholar
  • 36 Laffont B, Corduan A, Plé H. et al. Activated platelets can deliver mRNA regulatory Ago2•microRNA complexes to endothelial cells via microparticles. Blood 2013; 122: 253-261.
    CrossrefPubMedGoogle Scholar