Thrombopoietin

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Thrombopoietin
Thrombopoietin

Existing structural data : 1V7M , 1V7N

Properties of human protein
Mass / length primary structure 314 to 353 amino acids
Isoforms 3
Identifier
Gene names THPO MGDF, MKCSF, ML, MPLLG, THCYT1, TPO
External IDs
Occurrence
Parent taxon Mammals
Orthologue
human House mouse
Entrez 7066 21832
Ensemble ENSG00000090534 ENSMUSG00000022847
UniProt P40225 P40226
Refseq (mRNA) NM_000460 NM_001173505
Refseq (protein) NP_000451 NP_001166976
Gene locus Chr 3: 184.37 - 184.38 Mb Chr 16: 20.73 - 20.73 Mb
PubMed search 7066 21832

Thrombopoietin or thrombopoietin ( gene name: THPO ) is a hormone that stimulates the formation and differentiation of platelet- forming cells, the megakaryocytes . In the context of thrombopoiesis, it is necessary for the production of blood platelets (thrombocytes).

Place of education and characteristics

Thrombopoietin is produced in the liver , kidneys and stromal cells of the bone marrow . It influences the course of hematopoiesis in various places and acts as a cytokine . In addition to the influence on megakaryocytes and the associated formation of platelets, thrombopoietin has an effect on haematopoietic stem cells .

Structure and genetics

Thrombopoietin is an approximately 78  kDa large glycoprotein . It consists of 332 to 335 amino acids . Part of the protein (N-terminal domain) is very similar to erythropoietin , the hormone necessary for the production of erythrocytes (red blood cells). The gene for thrombopoietin is located on the long arm of chromosome 3 (q26.3–27).

regulation

The hormonal control circuit of thrombopoietin differs from that of most other hormones because it is controlled by the number of available receptors. The formation of thrombopoietin promotes platelet formation. These are able to bind the hormone circulating in the blood through a thrombopoietin receptor located on their surface . In this way, less thrombopoietin is available for the formation of new platelets.

Diagnostics and medical application

The level of thrombopoietin in the blood is used as diagnostic evidence. So it correlates inversely proportionally with the amount of platelets and megakaryocytes. A low thrombopoietin level can therefore be observed with high platelet counts. This, in turn, is reflected in a lower proportion of newly formed megakaryocytes. Inflammation, infection, liver failure or haematological disorders, on the other hand, can lead to unexpectedly high or low levels of thrombopoietin.

In the case of a congenital or chemotherapy- induced deficiency of thrombocytes thrombocytopenia , thrombopoietin could be important as a drug to stimulate the formation of new ones . Thrombopoietin produced biotechnologically, i.e. recombinantly, is the subject of clinical research, but has so far not shown any significant effects. More promising are thrombopoietin receptor agonists, which are already being clinically tested.

further reading

  • Warren S. Alexander and Craig Hyland: Thrombopoietin Bioassay. In: JM Gibbins and MP Mahaut-Smith (eds.): Platelets and Megakaryocytes: Volume 1: Functional Assays (Methods in Molecular Biology) 1st ed., Humana Press, Totowa, 2004. ISBN 1588291014 . P. 347ff

Individual evidence

  1. Homologues at OMA
  2. Kaushansky K : Thrombopoietin the primary regulator of platelet production . In: Trends Endocrinol. Metab. . 8, No. 2, March 1997, pp. 45-50. PMID 18406785 .
  3. McIntosh B, Kaushansky K : Transcriptional regulation of bone marrow thrombopoietin by platelet proteins . In: Exp. Hematol. . 36, No. 7, July 2008, pp. 799-806. doi : 10.1016 / j.exphem.2008.02.012 . PMID 18410987 . PMC 2517608 (free full text).
  4. Samtani MN, Perez-Ruixo JJ, Brown KH, Cerneus D, Molloy CJ: Pharmacokinetic and pharmacodynamic modeling of pegylated thrombopoietin mimetic peptide (PEG-TPOm) after single intravenous dose administration in healthy subjects . In: J Clin Pharmacol . 49, No. 3, March 2009, pp. 336-50. doi : 10.1177 / 0091270008329559 . PMID 19246731 .
  5. Liem-Moolenaar M, Cerneus D, Molloy CJ, et al. : Pharmacodynamics and pharmacokinetics of the novel thrombopoietin mimetic peptide RWJ-800088 in humans . In: Clin Pharmacol Ther . 84, No. 4, October 2008, pp. 481-7. PMID 19238653 .