Disease relevance of Thpo

• However, reactive thrombocytosis of inflammatory disease is accompanied by elevated TPO levels [1].
• The reciprocal relationship of thrombopoietin (c-Mpl ligand) to changes in the platelet mass during busulfan-induced thrombocytopenia in the rabbit [2].
• By comparing the receptor action in different cell lines, we observed that in human hepatoma cells the signaling of c-mpI was 100-fold less sensitive to TPO than in rat hepatoma cells [3].
• METHODS: A replication-deficient adenovirus or an adeno-associated virus containing a chimeric promoter composed of 5 glucocorticoid response elements and the murine thrombopoietin complementary DNA (AdGRE.mTPO or AAVGRE.mTPO) was administered to the hearts of Sprague-Dawley rats [4].
• The mechanisms by which levels of TPO mRNA are regulated in cirrhosis have not been elucidated [5].

High impact information on Thpo

• Thrombopoietin also induced tyrosine phosphorylation of Vav in FDCP-2 cells, genetically engineered to express human c-Mpl (FDCP-hMpl5) [6].
• Thrombopoietin has an essential role in megakaryopoiesis and thrombopoiesis [6].
• Thrombopoietin and thrombin induce tyrosine phosphorylation of Vav in human blood platelets [6].
• Because the apparent molecular weight of a major tyrosine phosphorylated protein in platelets stimulated by thrombopoietin is approximately 85 to 95 kD, we examined the possibility that this could be Vav, a 95-kD proto-oncogene product [6].
• Our data suggest that thrombopoietin and other agonists may induce tyrosine phosphorylation of Vav by different mechanisms and Vav may also be involved in signaling during platelet aggregation by its redistribution to the cytoskeleton [6].

Chemical compound and disease context of Thpo

• The level of thrombopoietin mRNA did not differ significantly in splenectomized cirrhotic rats before or after administration of dimethylnitrosamine, but was lower than that in splenectomized rats without cirrhosis [7].

Biological context of Thpo

• Overlapping cDNA clones encoding rat thrombopoietin (TPO) were isolated from liver-derived cell line cDNA libraries and the nucleotide sequences were determined [8].
• When platelets were transfused into thrombocytopenic rabbits near the time of their platelet count nadir, the elevated levels of thrombopoietin decreased [2].
• These results confirm that thrombopoietin is the humoral mediator of megakaryocytopoiesis and suggest that the platelet mass may directly play a role in regulating the circulating levels of this factor [2].
• Signal transduction by the receptors for thrombopoietin (c-mpL) and interleukin-3 in hematopoietic and nonhematopoietic cells [3].
• Dual effects of adenovirus-mediated thrombopoietin gene transfer on hepatic oval cell proliferation and platelet counts [9].

Anatomical context of Thpo

• The plasma concentration of thrombopoietin (TPO) in general is inversely related to the mass of platelets and megakaryocytes [1].
• To see whether this molecule possessed the physiologic characteristics necessary to mediate the feed-back loop between blood platelets and the bone marrow megakaryocytes, we determined the relationship between blood levels of thrombopoietin and changes in the circulating platelet mass [2].
• In this study, we found the production of TPO by hepatocytes isolated with the collagenase perfusion method from both normal and thrombocytopenic rats, by a two-step fractionation of hepatocyte culture medium (CM) [10].
• GpIIb/IIIa+ subpopulation of rat megakaryocyte progenitor cells exhibits high responsiveness to human thrombopoietin [11].
• In normal rats, there were high levels of TPO mRNA in the liver and kidney, intermediate levels in the brain and large intestine, and low levels in the skeletal muscle and small intestine [12].

Associations of Thpo with chemical compounds

• LPS-treated rats showed a significant increase in hepatic TPO mRNA concentration [1].
• We subsequently measured the level of thrombopoietin in the circulation over the entire time course after the administration of busulfan [2].
• Oval cells expressed c-Mpl, a receptor for TPO as well as immature hematopoietic and hepatocytic surface markers such as CD34 and AFP [9].
• Four cysteine residues and two of four N-glycosylation sites that are conserved among species were also found at the corresponding positions in feline TPO [13].
• Thrombopoietin protects against in vitro and in vivo cardiotoxicity induced by doxorubicin [14].

Regulatory relationships of Thpo

• Hepatocyte growth factor/scatter factor enhances the thrombopoietin mRNA expression in rat hepatocytes and cirrhotic rat livers [15].

Other interactions of Thpo

• Thrombopoietin expression in normal and hypobaric hypoxia-induced thrombocytopenic rats [12].

Analytical, diagnostic and therapeutic context of Thpo

• After 6 h, total RNA from liver and kidney was reverse transcribed and analyzed by competitive PCR for TPO and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) [1].
• Northern blot analysis showed that TPO mRNA was expressed mainly in liver among the various organs tested [10].
• TPO-active fraction eluted from the final reverse-phase column was separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), extracted from the gel, and assayed [10].
• Using reverse transcriptase-polymerase chain reaction (RT-PCR), we detected the expression of TPO mRNA in hepatocytes, three hepatoma cell lines, normal rat liver, and X-irradiated rat liver [10].
• In this study, we examined the in vitro and in vivo biological activity of TPO and its therapeutic efficacy in experimental animal models [16].

References