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Tytuł oryginału:
Thrombopoietin, but not cytokines binding to gp130 protein-coupled receptors, activates MAPKp42/44, AKT, and STAT proteins in normal human CD34+ cells, megakaryocytes, and platelets.
Autorzy:
Majka
Marcin,
Ratajczak
Janina,
Villaire
Gaston,
Kubiczek
Krystyna,
Marquez
Leah A.,
Janowska-Wieczorek
Anna,
Ratajczak
Mariusz Z.
Źródło:
Exp. Hematol. 2002: 30 (7) s.751-760, il., tab., bibliogr. 51 poz.
Sygnatura GBL:
305,749
Hasła klasyfikacyjne GBL:
hematologia
Typ dokumentu:
praca doświadczalna
praca opublikowana za granicą
tytuł obcojęzyczny
Wskaźnik treści:
ludzie
Streszczenie angielskie:
Objective: The development of megakaryocytes is regulated by thrombopoietin (TPO), which binds to the c-mpl receptor, and by several other cytokines such as interleukin (IL)-6, IL-11, leukemia inhibitory factor (LIF), cilliary neurotropic factor (CNTF), and oncostatin (OSM), which bind to gp130 protein-coupled receptors. We attempted to identify signal transduction pathways activated by these factors in normal human megakaryocytes. Materials and methods: To better understand the role of these factors in normal human megakaryopoiesis we studied their effect on 1) purified human bone marrow-derived CD34+ cells, 2) human ŕIIbá3+ cells (shown by immunophenotypical and morphological criteria to be megakaryoblasts), which had been expanded ex vivo from CD34+ cells in chemically defined artificial serum, and 3) gel-filtered human peripheral blood platelets. Further, in an attempt to correlate the influence of these factors on cell proliferation and survival activation of signal transduction pathways, we evaluated their effect on the phosphorylation of MAPK p42/44 and activation of PI-3K-AKT and JAK-STAT proteins in these various cell types. Results: Using serum-free liquid cultures, we found that only TPO and IL-6 protected CD34+ cells and megakaryocytes from undergoing apoptosis (decrease in annexin-V binding, PARP cleavage, and activation of caspase-3). Moreover, only TPO when used alone and IL-6 only when used in combination with TPO, stimulated the growth of human colony-forming unitmegakarocytes (CFU-Meg) in semisolid serum-free medium...
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