title: Hepatocyte growth factor accelerates thrombopoiesis in transgenic mice.
abstract: Hepatocyte growth factor (HGF) is one of the potent growth factors for liver regeneration and has a strong effect on epithelial and nonepithelial cells. As one of the pleiotropic functions, HGF acts as a hematopoietic regulator in the proliferation and differentiation of hematopoietic progenitors. However, the effect of HGF on the thrombopoietic function remains unclear. The correlation between HGF and thrombopoiesis was investigated in transgenic (TG) mice overexpressing murine HGF controlled by the murine HGF by the metallothionein promoter. Furthermore, the mechanism of thrombocytosis induced by HGF in vitro was analyzed in hepatoma cell line HepG2. Both the platelet count and the serum thrombopoietin (TPO) concentration were significantly higher in TG than in the wild type (WT) control mice. In the liver and spleen, the expression of TPOmRNA in TG was higher than that in WT by real-time polymerase chain reaction. The expressions of transcriptional factor of TPO, GABP-alpha/beta were more increased in TG liver compared to WT. In an in vitro study, HGF induced TPO and GABP-alpha/beta expression and enhanced TPO promoter activity. Therefore, HGF induced thrombopoiesis accompanied with the overexpression of TPO through GABP stimulation.
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kosone
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takagi
authors.forename: Norio
authors.initials: N
authors.lastname: Horiguchi
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Toyoda
authors.forename: Naondo
authors.initials: N
authors.lastname: Sohara
authors.forename: Satoru
authors.initials: S
authors.lastname: Kakizaki
authors.forename: Ken
authors.initials: K
authors.lastname: Sato
authors.forename: Uichi
authors.initials: U
authors.lastname: Nishiyama
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kuwaki
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori
mesh_terms: D000818:Animals; D001835:Body Weight; D045744:Cell Line, Tumor; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D034061:Thrombopoiesis / Q000502:physiology*; D013926:Thrombopoietin / Q000097:blood / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D013926:Thrombopoietin