Hepatocyte growth factor/scatter factor enhances the thrombopoietin mRNA expression in rat hepatocytes and cirrhotic rat livers

Background: Although thrombopoietin (TPO) is mainly produced in the liver, the regulatory mechanism of TPO gene expression in hepatocytes remains uncl ear. The role of TPO in thrombocytopenia associated with liver cirrhosis ha s not been identified. Methods: We examined the effects of various growth factors and cytokines on TPO mRNA expression in adult rat hepatocytes in primary cultures using a s emiquantitative reverse transcription-polymerase chain reaction assay. Results: Among them, only hepatocyte growth factor/scatter factor (HGF/SF) enhanced TPO mRNA expression; other growth factors (epidermal growth factor and transforming growth factor-beta) and cytokines (erythropoietin, granul ocyte-colony stimulating factor, granulocyte-macrophage-colony stimulating factor, interleukin (IL)-3, IL-6 and interferon-gamma) did not. Next, we ex amined TPO mRNA expression in the livers of rats with CCl4-induced cirrhosi s, the effects of HGF/SF on hepatic TPO mRNA expression and peripheral plat elet and bone marrow megakaryocyte counts in the cirrhotic rats. In the cir rhotic rats, both the peripheral platelet count and TPO mRNA expression in the livers were markedly decreased compared with those of the normal rats. The administration of HGF/SF to the cirrhotic rats stimulated TPO mRNA expr ession in the livers and resulted in significant increases of peripheral pl atelets and bone marrow megakaryocytes. Conclusions: These results suggest that HGF/SF is a possible regulatory fac tor for TPO gene expression and that HGF/SF increases platelet production t hrough an enhancement of TPO mRNA expression in the livers of cirrhotic rat s. (C) 2000 Blackwell Science Asia Pty Ltd.