Hepatic Thrombopoietin Mrna Levels in Acute and Chronic Liver Failure of Childhood

Abstract

The liver is the main production site of the hormone thrombopoietin (TPO), the major regulator of megakaryopoiesis. To investigate the role of an impaired TPO gene expression in the pathogenesis of thrombocytopenia in pediatric patients suffering from liver failure, we measured hepatic TPO mRNA in children with acute or chronic end-stage liver disease undergoing orthotopic liver transplantation. Tissue samples for RNA extraction were obtained from 12 children with compensated cirrhosis (CC), 22 children with decompensated cirrhosis (DC), and 9 children with acute liver failure (ALF). The glycoprotein hormone, thrombopoietin (TPO), is the major regulator of megakaryopoiesis and platelet production. 1,2 Northern blot analyses have demonstrated that TPO mRNA is expressed predominantly in liver, and to a minor degree, in kidney, spleen, and brain. 3,4 A recent report from this laboratory has shown that hepatic TPO mRNA accounts for 94% of the total in the perinatal period. 5 In situ hybridization studies have localized TPO mRNA in parenchymal cells of the human 6 and murine 7 liver. Hepatocytes appear to produce TPO at a constant rate. The plasma concentration of the hormone is regulated by the degree of receptor-mediated binding and degradation of TPO by platelets and, in all likelihood, megakaryocytes.

Non-Hypersplenism Causes of Peripheral Cytopenias in Patients with Cirrhotic Portal Hypertension: A Review

“…In cirrhosis, there is a decrease in functional hepatocytes. A correlation between decreases in serum levels of TPO with platelet counts has been found by Wolber et al [16] during transition from compensated to decompensated cirrhosis.…”

Thrombopoietin in Acute Liver Failure

“…Extrahepatic TPO production is thought to be limited 3 but has not been studied in ALF; a clinical study found decreased hepatic TPO messenger RNA levels in children with ALF compared with cirrhosis. 13 We suggest that studying hepatic versus extrahepatic TPO production in animal models of ALF might clarify this issue.…”

Regulating billions of blood platelets: glycans and beyond

“…43 Further, a number of inflammatory states (eg, ulcerative colitis, rheumatoid arthritis, and ovarian cancer) are associated with increased blood TPO levels and thrombocytosis. 1,38,[44][45][46][47][48][49][50][51] This inflammation-induced increase in TPO expression is mediated by IL-6, which stimulates hepatic TPO messenger RNA (mRNA) expression and production both in hepatocytes in vivo and in hepatoma HepG2 and Hep3B cells in vitro. 49,50,52,53 If hepatic TPO regulation by IL-6 is now well characterized, the ligand-receptor pair regulating hepatic TPO production at steady state has remained elusive.…”