Background: Although thrombopoietin (TPO) is mainly produced in the liver, the regulatory mechanism of TPO gene expression in hepatocytes remains unclear. The role of TPO in thrombocytopenia associated with liver cirrhosis has 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 semiquantitative 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-β) and cytokines (erythropoietin, granulocyte-colony stimulating factor, granulocyte-macrophage-colony stimulating factor, interleukin (IL)-3, IL-6 and interferon-γ) did not. Next, we examined TPO mRNA expression in the livers of rats with CCl4-induced cirrhosis, the effects of HGF/SF on hepatic TPO mRNA expression and peripheral platelet and bone marrow megakaryocyte counts in the cirrhotic rats. In the cirrhotic 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 expression in the livers and resulted in significant increases of peripheral platelets and bone marrow megakaryocytes.
Conclusions: These results suggest that HGF/SF is a possible regulatory factor for TPO gene expression and that HGF/SF increases platelet production through an enhancement of TPO mRNA expression in the livers of cirrhotic rats.