title: hGH promotes megakaryocyte differentiation and exerts a complementary effect with c-Mpl ligands on thrombopoiesis.
abstract: Human growth hormone (hGH) is known to play a functional role in regulating hematopoiesis, although its direct effect on thrombopoiesis is unclear. In this study, we show for the first time that hGH has a distinct capacity to promote the differentiation of human primary megakaryocytes derived from umbilical cord blood CD34(+) cells. In particular, hGH is potent in facilitating proplatelet formation and platelet production from cultured megakaryocytes. The stage- and time-specific activations of extracellular signal-regulated kinase 1/2 and protein kinase B signaling pathways are involved in the action of hGH. Fusion with hGH enhances the effect of a tandem dimer of thrombopoietin mimetic peptide (dTMP) on thrombopoiesis, manifested by a significant acceleration and increase of platelet production, indicating that hGH may exert a complementary and synergistic effect with c-Mpl ligands on thrombopoiesis. Accordingly, the administration of dTMP-growth hormone fusion protein led to a rapid platelet recovery in mice with severe thrombocytopenia induced by 6.5 Gy total body irradiation, thereby markedly abridging the duration of thrombocytopenia crisis (platelets <150 × 10(9)/L), in comparison with high doses of dTMP. These findings demonstrate the functional role of growth hormone in promoting thrombopoiesis and provide a promising avenue for the treatment of severe thrombocytopenia.
authors.affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.forename: Song
authors.initials: S
authors.lastname: Wang
authors.forename: Mingqiang
authors.initials: M
authors.lastname: Shen
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhang
authors.forename: Shilei
authors.initials: S
authors.lastname: Chen
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
authors.forename: Mo
authors.initials: M
authors.lastname: Chen
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Zeng
authors.forename: Aiping
authors.initials: A
authors.lastname: Wang
authors.forename: Jinghong
authors.initials: J
authors.lastname: Zhao
authors.forename: Tianmin
authors.initials: T
authors.lastname: Cheng
authors.forename: Yongping
authors.initials: Y
authors.lastname: Su
authors.forename: Junping
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D008297:Male; D008533:Megakaryocytes / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D053628:Receptors, Thrombopoietin / Q000819:agonists*; D034061:Thrombopoiesis / Q000187:drug effects*
chemical_list: D008024:Ligands; D010455:Peptides; D053628:Receptors, Thrombopoietin; C515728:thrombopoietin mimetic peptide; D019382:Human Growth Hormone; C082218:MPL protein, human