Expression of hepatic thrombopoietin mRNA in primary cultured hepatocytes and in rats with acute liver injury or bone marrow suppression with or without cirrhosis

Background and Aims: The main causes of thrombocytopenia in cirrhosis are t hought to be platelet destruction and the reduction of thrombopoietin (TPO) expression in the liver. The mechanisms by which levels of TPO mRNA are re gulated in cirrhosis have not been elucidated. In this study, we investigat ed some possible mechanisms. Methods: We used three experimental models: bone marrow suppression, acute liver injury and primary cultured hepatocytes. We used northern blots to as sess the kinetics of TPO mRNA expression in the livers of irradiated rats ( with and without cirrhosis) in acute liver injury and in primary cultured h epatocytes treated with hepatotoxin or cytokines. Results: Although the bone marrow was hypocellular, there was no apparent e nhancement of TPO mRNA expression in the irradiated rats with cirrhotic liv ers compared with the unirradiated rats with cirrhotic livers. There were n o conspicuous changes in hepatic TPO mRNA expression between the livers of the control rats and the three models of acute liver injury. There were no conspicuous changes in the levels of TPO mRNA between control hepatocytes a nd hepatocytes treated with hepatotoxin or cytokines. Conclusions: Our results suggest that bone marrow is not a regulator of hep atic TPO production in cirrhosis. The reduced TPO mRNA expression found in cirrhotic rats may not result merely from serious cellular damage; it may b e associated with cirrhosis-specific regulatory mechanisms for the expressi on of the TPO gene. Further studies are needed to search for other factors that may induce reduced TPO expression. (C) 2000 Blackwell Science Asia Pty Ltd.