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{{Infobox_gene}}
{{PBB_Controls
'''Thrombopoietin''' (THPO) also known as '''megakaryocyte growth and development factor''' (MGDF) is a [[protein]] that in humans is encoded by the ''THPO'' [[gene]].
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| update_protein_box = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
Thrombopoietin is a [[glycoprotein]] [[hormone]] produced by the [[liver]] and [[kidney]] which regulates the production of [[platelet]]s. It stimulates the production and differentiation of [[megakaryocyte]]s, the bone marrow cells that bud off large numbers of [[platelets]].<ref name=Kaushansky2006>{{cite journal |author=Kaushansky K |title=Lineage-specific hematopoietic growth factors |journal=N. Engl. J. Med. |volume=354 |issue=19 |pages=2034–45 |year=2006 |pmid=16687716 |doi=10.1056/NEJMra052706}}</ref>
{{GNF_Protein_box
| image = PBB_Protein_THPO_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1v7m.
| PDB = {{PDB2|1v7m}}, {{PDB2|1v7n}}
| Name = Thrombopoietin (myeloproliferative leukemia virus oncogene ligand, megakaryocyte growth and development factor)
| HGNCid = 11795
| Symbol = THPO
| AltSymbols =; MGC163194; MGDF; MKCSF; ML; MPLLG; TPO
| OMIM = 600044
| ECnumber = 
| Homologene = 398
| MGIid = 101875
| GeneAtlas_image1 = PBB_GE_THPO_211155_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_THPO_211154_at_tn.png
| GeneAtlas_image3 = PBB_GE_THPO_211831_s_at_tn.png
| Function = {{GNF_GO|id=GO:0005125 |text = cytokine activity}} {{GNF_GO|id=GO:0005179 |text = hormone activity}} {{GNF_GO|id=GO:0008083 |text = growth factor activity}}
| Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}} {{GNF_GO|id=GO:0005615 |text = extracellular space}}
| Process = {{GNF_GO|id=GO:0007275 |text = multicellular organismal development}} {{GNF_GO|id=GO:0008283 |text = cell proliferation}} {{GNF_GO|id=GO:0030099 |text = myeloid cell differentiation}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 7066
    | Hs_Ensembl = ENSG00000090534
    | Hs_RefseqProtein = NP_954698
    | Hs_RefseqmRNA = NM_199228
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 3
    | Hs_GenLoc_start = 185572995
    | Hs_GenLoc_end = 185578626
    | Hs_Uniprot = P40225
    | Mm_EntrezGene = 21832
    | Mm_Ensembl = ENSMUSG00000022847
    | Mm_RefseqmRNA = NM_009379
    | Mm_RefseqProtein = NP_033405
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 16
    | Mm_GenLoc_start = 20638951
    | Mm_GenLoc_end = 20642402
    | Mm_Uniprot = Q543R9
  }}
}}


'''Thrombopoietin (leukemia virus oncogene ligand, megakaryocyte growth and development factor)''', also known as '''THPO''', is a [[glycoprotein]] [[hormone]] produced mainly by the [[liver]] and the [[kidney]] that regulates the production of [[platelet]]s by the [[bone marrow]]. It stimulates the production and differentiation of [[megakaryocyte]]s, the bone marrow cells that fragment into large numbers of [[platelets]].<ref name=Kaushansky2006>{{cite journal |author=Kaushansky K |title=Lineage-specific hematopoietic growth factors |journal=N. Engl. J. Med. |volume=354 |issue=19 |pages=2034–45 |year=2006 |pmid=16687716 |doi=10.1056/NEJMra052706}}</ref>
Megakaryocytopoiesis is the cellular development process that leads to platelet production. The protein encoded by this gene is a humoral growth factor necessary for [[megakaryocyte]] proliferation and maturation, as well as for thrombopoiesis. This protein is the ligand for MLP/C_MPL, the product of myeloproliferative leukemia virus oncogene.<ref name="entrez">{{cite web | title = Entrez Gene: THPO thrombopoietin (myeloproliferative leukemia virus oncogene ligand, megakaryocyte growth and development factor)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7066| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Genetics ==
{{PBB_Summary
The thrombopoietin [[gene]] is located on the long arm of [[chromosome 3]] (q26.3-27). Abnormalities in this gene occur in some [[hereditary]] forms of [[thrombocytosis]] (high platelet count) and in some cases of [[leukemia]]. The first 155 [[amino acid]]s of the protein share [[homology (biology)|homology]] with [[erythropoietin]].<ref>{{OMIM|600044}}</ref>
| section_title =
| summary_text = Megakaryocytopoiesis is the cellular development process that leads to platelet production. The protein encoded by this gene is a humoral growth factor that is necessary for megakaryocyte proliferation and maturation, as well as for thrombopoiesis. This protein is the ligand for MLP/C_MPL, the product of myeloproliferative leukemia virus oncogene.<ref name="entrez">{{cite web | title = Entrez Gene: THPO thrombopoietin (myeloproliferative leukemia virus oncogene ligand, megakaryocyte growth and development factor)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7066| accessdate = }}</ref>
}}


==Genetics==
== Function and regulation ==
The thrombopoietin [[gene]] is located on the long arm of [[chromosome 3]] (q26.3-27). Abnormalities in this gene occur in some [[hereditary]] forms of [[thrombocytosis]] (high platelet count) and in some cases of [[leukemia]]. Thrombopoietin shares its first 153 [[amino acid]]s with [[erythropoietin]].<ref>{{OMIM|600044}}</ref>
Thrombopoietin is produced in the liver by both parenchymal cells and [[Liver sinusoid|sinusoidal]] endothelial cells, as well as in the kidney by proximal convoluted tubule cells. Small amounts are also made by [[striated muscle]] and bone marrow stromal cells.<ref name=Kaushansky2006/> In the liver, its production is augmented by [[interleukin 6]] (IL-6).<ref name=Kaushansky2006/> However, the liver and the bone marrow stromal cells are the primary sites of thrombopoietin production.


==Function and regulation==
Thrombopoietin regulates the differentiation of [[megakaryocyte]]s and [[platelets]], but studies on the removal of the thrombopoietin receptor show that its effects on [[hematopoiesis]] are more versatile.<ref name=Kaushansky2006/>
In the liver it is produced by parenchymal cells and sinusoidal endothelial cells. In the kidney it is made by proximal convoluted tubule cells. Along with these it is made by [[striated muscle]] and stromal cells in the [[bone marrow]].<ref name=Kaushansky2006/> In the liver, its production is augmented by [[interleukin 6]] (IL-6).<ref name=Kaushansky2006/>


Thrombopoietin regulates the differentiation of [[megakaryocyte]]s and [[platelets]], but studies on the removal of the thrombopoeitin receptor show that its effects on [[hematopoiesis]] are more versatile<ref name=Kaushansky2006/>.
Its negative feedback is different from that of most hormones in [[endocrinology]]: The effector regulates the hormone directly. Thrombopoietin is bound to the surface of platelets by the mpl receptor ([[CD 110]]) and destroyed, thereby reducing megakaryocyte exposure to the hormone.<ref name=Kaushansky2006/> Therefore, the rising and dropping platelet concentrations regulate the thrombopoietin levels. Low platelets lead a higher degree of thrombopoietin exposure to the undifferentiated bone marrow cells, leading to differentiation into [[megakaryocyte]]s and further maturation of these cells. On the other hand, high platelet concentrations lead to less availability of thrombopoietin to megakaryocytes.


Its negative [[feedback]] is different from most hormones in [[endocrinology]]: the effector regulates the hormone directly. Thrombopoeitin is bound to the surface of platelets by the mpl receptor (CD 110) and destroyed, thereby reducing megakaryocyte exposure to the hormone.<ref name=Kaushansky2006/>
== Therapeutic use ==
Despite numerous trials, thrombopoietin has not been found to be useful therapeutically. Theoretical uses include the procurement of platelets for donation,<ref>{{cite journal  |vauthors=Kuter DJ, Goodnough LT, Romo J, etal |title=Thrombopoietin therapy increases platelet yields in healthy platelet donors |journal=Blood |volume=98 |issue=5 |pages=1339–45 |year=2001 |pmid=11520780 |url=http://www.bloodjournal.org/cgi/content/full/98/5/1339 |doi=10.1182/blood.V98.5.1339}}</ref> and recovery of platelet counts after myelosuppressive [[chemotherapy]].<ref name=Kaushansky2006/>


==Therapeutic use==
Trials of a modified recombinant form, megakaryocyte growth and differentiation factor (MGDF), were stopped when healthy volunteers developed autoantibodies to endogenous thrombopoietin and then developed thrombocytopenia.<ref name="pmid11719360">{{cite journal |vauthors=Li J, Yang C, Xia Y, Bertino A, Glaspy J, Roberts M, Kuter DJ | title = Thrombocytopenia caused by the development of antibodies to thrombopoietin | journal = Blood | volume = 98 | issue = 12 | pages = 3241–8 |date=December 2001 | pmid = 11719360 | doi = 10.1182/blood.V98.12.3241 }}</ref> [[Romiplostim]] and [[Eltrombopag]], structurally different compounds that stimulate the same pathway, are used instead.<ref name="pmid21864167">{{cite journal |vauthors=Imbach P, Crowther M | title = Thrombopoietin-receptor agonists for primary immune thrombocytopenia | journal = N. Engl. J. Med. | volume = 365 | issue = 8 | pages = 734–41 |date=August 2011 | pmid = 21864167 | doi = 10.1056/NEJMct1014202 }}</ref>
Despite numerous trials, thrombopoeitin is not used therapeutically. Theoretical uses include the procurement of platelets for donation<ref>{{cite journal |author=Kuter DJ, Goodnough LT, Romo J, ''et al'' |title=Thrombopoietin therapy increases platelet yields in healthy platelet donors |journal=Blood |volume=98 |issue=5 |pages=1339–45 |year=2001 |pmid=11520780 |url=http://www.bloodjournal.org/cgi/content/full/98/5/1339 |doi=10.1182/blood.V98.5.1339}}</ref>, recovery of platelet counts after myelosuppressive [[chemotherapy]].<ref name=Kaushansky2006/>


A modified recombinant form, termed "megakaryocyte growth and differentiation factor" (MGDF), caused a paradoxical reaction, delaying the development of therapeutic thrombopoietin. A quadrivalent peptide analogue is undergoing development, as well as several [[small molecule]] agents,<ref name=Kaushansky2006/> including several non-peptide ligands of ''c-Mpl'', which act as thrombopoietin analogues.<ref>{{cite journal |author=Nakamura T, Miyakawa Y, Miyamura A, ''et al'' |title=A novel nonpeptidyl human c-Mpl activator stimulates human megakaryopoiesis and thrombopoiesis |journal=Blood |volume=107 |issue=11 |pages=4300–7 |year=2006 |pmid=16484588 |doi=10.1182/blood-2005-11-4433}}</ref><ref>{{cite journal |author=Jenkins JM, Williams D, Deng Y, ''et al'' |title=Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist |journal=Blood |volume=109 |issue=11 |pages=4739–41 |year=2007 |pmid=17327409 |doi=10.1182/blood-2006-11-057968}}</ref>
A quadrivalent peptide analogue is being investigated, as well as several [[small molecule|small-molecule]] agents,<ref name=Kaushansky2006/> and several non-peptide ligands of ''c-Mpl'', which act as thrombopoietin analogues.<ref>{{cite journal |vauthors=Nakamura T, Miyakawa Y, Miyamura A, etal |title=A novel nonpeptidyl human c-Mpl activator stimulates human megakaryopoiesis and thrombopoiesis |journal=Blood |volume=107 |issue=11 |pages=4300–7 |year=2006 |pmid=16484588 |doi=10.1182/blood-2005-11-4433}}</ref><ref>{{cite journal |vauthors=Jenkins JM, Williams D, Deng Y, etal |title=Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist |journal=Blood |volume=109 |issue=11 |pages=4739–41 |year=2007 |pmid=17327409 |doi=10.1182/blood-2006-11-057968}}</ref>


==History==
== Discovery ==
Thrombopoietin was cloned by five independent groups in 1994.  Before its identification, its function has been hypothesized for as much as 30 years as being linked to the [[cell surface receptor]] ''c-Mpl'', and in older publications ''thrombopoietin'' is described as ''c-Mpl ligand'' (the agent that binds to the c-Mpl molecule).  Thrombopoietin is one of the Class I hematopoietic cytokines.<ref name=Kaushansky2006/>
Thrombopoietin was cloned by five independent teams in 1994.  Before its identification, its function has been hypothesized for as much as 30 years as being linked to the [[cell surface receptor]] ''c-Mpl'', and in older publications ''thrombopoietin'' is described as ''c-Mpl ligand'' (the agent that binds to the c-Mpl molecule).  Thrombopoietin is one of the Class I hematopoietic cytokines.<ref name=Kaushansky2006/>


==References==
==See also==
{{reflist|2}}
*[[Thrombopoietic agent]]
==Further reading==
 
== References ==
{{reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal |vauthors=Hitchcock IS, Kaushansky K | title = Thrombopoietin from beginning to end | journal = Br. J. Haematol. | volume = 165 | issue = 2 | pages = 259–68 | year = 2014 | pmid = 24499199 | doi = 10.1111/bjh.12772 }}
| citations =
* {{cite journal | author = Wörmann B | title = Clinical indications for thrombopoietin and thrombopoietin-receptor agonists | journal = Transfus Med Hemother | volume = 40 | issue = 5 | pages = 319–25 | year = 2013 | pmid = 24273485 | pmc = 3822275 | doi = 10.1159/000355006 }}
*{{cite journal | author=Kato T, Matsumoto A, Ogami K, ''et al.'' |title=Native thrombopoietin: structure and function. |journal=Stem Cells |volume=16 |issue= 5 |pages= 322-8 |year= 1999 |pmid= 9766811 |doi=  }}
* {{cite journal | author = Kuter DJ | title = The biology of thrombopoietin and thrombopoietin receptor agonists | journal = Int. J. Hematol. | volume = 98 | issue = 1 | pages = 10–23 | year = 2013 | pmid = 23821332 | doi = 10.1007/s12185-013-1382-0 }}
*{{cite journal  | author=Kato T |title=Protein characteristics of thrombopoietin. |journal=Stem Cells |volume=14 Suppl 1 |issue=  |pages= 139-47 |year= 2000 |pmid= 11012214 |doi=  }}
* {{cite journal |vauthors=Lupia E, Goffi A, Bosco O, Montrucchio G | title = Thrombopoietin as biomarker and mediator of cardiovascular damage in critical diseases | journal = Mediators Inflamm. | volume = 2012 | issue = | pages = 390892 | year = 2012 | pmid = 22577249 | pmc = 3337636 | doi = 10.1155/2012/390892 }}
*{{cite journal  | author=Geddis AE, Linden HM, Kaushansky K |title=Thrombopoietin: a pan-hematopoietic cytokine. |journal=Cytokine Growth Factor Rev. |volume=13 |issue= 1 |pages= 61-73 |year= 2002 |pmid= 11750880 |doi=    | doi=10.1016/S1359-6101(01)00030-2}}
* {{cite journal |vauthors=Liebman HA, Pullarkat V | title = Diagnosis and management of immune thrombocytopenia in the era of thrombopoietin mimetics | journal = Hematology Am Soc Hematol Educ Program | volume = 2011 | issue = | pages = 384–90 | year = 2011 | pmid = 22160062 | doi = 10.1182/asheducation-2011.1.384 }}
*{{cite journal  | author=von dem Borne A, Folman C, van den Oudenrijn S, ''et al.'' |title=The potential role of thrombopoietin in idiopathic thrombocytopenic purpura. |journal=Blood Rev. |volume=16 |issue= 1 |pages= 57-9 |year= 2002 |pmid= 11913997 |doi= 10.1054/blre.2001.0184 }}
*{{cite journal  | author=Kaushansky K |title=Thrombopoietin: from theory to reality. |journal=Int. J. Hematol. |volume=76 Suppl 1 |issue= |pages= 343-5 |year= 2003 |pmid= 12430879 |doi=  }}
*{{cite journal  | author=Kralovics R, Skoda RC |title=Molecular pathogenesis of Philadelphia chromosome negative myeloproliferative disorders. |journal=Blood Rev. |volume=19 |issue= 1 |pages= 1-13 |year= 2005 |pmid= 15572213 |doi= 10.1016/j.blre.2004.02.002 }}
*{{cite journal | author=Migliaccio AR, Rana RA, Vannucchi AM, Manzoli FA |title=Role of thrombopoietin in mast cell differentiation. |journal=Ann. N. Y. Acad. Sci. |volume=1106 |issue=  |pages= 152-74 |year= 2007 |pmid= 17468237 |doi= 10.1196/annals.1392.024 }}
*{{cite journal  | author=Foster DC, Sprecher CA, Grant FJ, ''et al.'' |title=Human thrombopoietin: gene structure, cDNA sequence, expression, and chromosomal localization. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=91 |issue= 26 |pages= 13023-7 |year= 1995 |pmid= 7809166 |doi=  }}
*{{cite journal  | author=Chang MS, McNinch J, Basu R, ''et al.'' |title=Cloning and characterization of the human megakaryocyte growth and development factor (MGDF) gene. |journal=J. Biol. Chem. |volume=270 |issue= 2 |pages= 511-4 |year= 1995 |pmid= 7822271 |doi=  }}
*{{cite journal  | author=Gurney AL, Kuang WJ, Xie MH, ''et al.'' |title=Genomic structure, chromosomal localization, and conserved alternative splice forms of thrombopoietin. |journal=Blood |volume=85 |issue= 4 |pages= 981-8 |year= 1995 |pmid= 7849319 |doi=  }}
*{{cite journal | author=Sohma Y, Akahori H, Seki N, ''et al.'' |title=Molecular cloning and chromosomal localization of the human thrombopoietin gene. |journal=FEBS Lett. |volume=353 |issue= 1 |pages= 57-61 |year= 1994 |pmid= 7926023 |doi=   | doi=10.1016/0014-5793(94)01008-0}}
*{{cite journal | author=Bartley TD, Bogenberger J, Hunt P, ''et al.'' |title=Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor Mpl. |journal=Cell |volume=77 |issue= 7 |pages= 1117-24 |year= 1994 |pmid= 8020099 |doi=    | doi=10.1016/0092-8674(94)90450-2}}
*{{cite journal  | author=de Sauvage FJ, Hass PE, Spencer SD, ''et al.'' |title=Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand. |journal=Nature |volume=369 |issue= 6481 |pages= 533-8 |year= 1994 |pmid= 8202154 |doi= 10.1038/369533a0 }}
*{{cite journal  | author=Kaushansky K, Lok S, Holly RD, ''et al.'' |title=Promotion of megakaryocyte progenitor expansion and differentiation by the c-Mpl ligand thrombopoietin. |journal=Nature |volume=369 |issue= 6481 |pages= 568-71 |year= 1994 |pmid= 8202159 |doi= 10.1038/369568a0 }}
*{{cite journal | author=Wendling F, Maraskovsky E, Debili N, ''et al.'' |title=cMpl ligand is a humoral regulator of megakaryocytopoiesis. |journal=Nature |volume=369 |issue= 6481 |pages= 571-4 |year= 1994 |pmid= 8202160 |doi= 10.1038/369571a0 }}
*{{cite journal  | author=Kato T, Ogami K, Shimada Y, ''et al.'' |title=Purification and characterization of thrombopoietin. |journal=J. Biochem. |volume=118 |issue= 1 |pages= 229-36 |year= 1996 |pmid= 8537317 |doi= }}
*{{cite journal  | author=Hoffman RC, Andersen H, Walker K, ''et al.'' |title=Peptide, disulfide, and glycosylation mapping of recombinant human thrombopoietin from ser1 to Arg246. |journal=Biochemistry |volume=35 |issue= 47 |pages= 14849-61 |year= 1997 |pmid= 8942648 |doi= 10.1021/bi961075b }}
*{{cite journal | author=Wiestner A, Schlemper RJ, van der Maas AP, Skoda RC |title=An activating splice donor mutation in the thrombopoietin gene causes hereditary thrombocythaemia. |journal=Nat. Genet. |volume=18 |issue= 1 |pages= 49-52 |year= 1998 |pmid= 9425899 |doi= 10.1038/ng0198-49 }}
*{{cite journal  | author=Kondo T, Okabe M, Sanada M, ''et al.'' |title=Familial essential thrombocythemia associated with one-base deletion in the 5'-untranslated region of the thrombopoietin gene. |journal=Blood |volume=92 |issue= 4 |pages= 1091-6 |year= 1998 |pmid= 9694695 |doi=  }}
}}
{{refend}}
{{refend}}


==External links==
==External links==
* [http://www.priory.com/med/thrombo.htm Longer summary on thrombopoietin]
* [http://www.priory.com/med/thrombo.htm Longer summary on thrombopoietin]


{{PDB Gallery|geneid=7066}}
{{Colony-stimulating factors}}
{{Colony-stimulating factors}}
{{Glycoproteins}}
{{Glycoproteins}}
{{Growth factor receptor modulators}}
{{Cytokine receptor modulators}}
[[Category:Growth factors]]
[[Category:Growth factors]]
 
[[Category:Thrombopoietin receptor agonists]]
[[de:Thrombopoetin]]
[[dv:ތްރޮމްބޯ ޕޮއިއިޓިން]]
[[lt:Trombopoetinas]]
[[pt:Trombopoietina]]
[[tr:Trombopoetin]]
{{WikiDoc Sources}}

Latest revision as of 16:18, 5 March 2018

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Orthologs
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Ensembl

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UniProt

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RefSeq (mRNA)

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View/Edit Human

Thrombopoietin (THPO) also known as megakaryocyte growth and development factor (MGDF) is a protein that in humans is encoded by the THPO gene.

Thrombopoietin is a glycoprotein hormone produced by the liver and kidney which regulates the production of platelets. It stimulates the production and differentiation of megakaryocytes, the bone marrow cells that bud off large numbers of platelets.[1]

Megakaryocytopoiesis is the cellular development process that leads to platelet production. The protein encoded by this gene is a humoral growth factor necessary for megakaryocyte proliferation and maturation, as well as for thrombopoiesis. This protein is the ligand for MLP/C_MPL, the product of myeloproliferative leukemia virus oncogene.[2]

Genetics

The thrombopoietin gene is located on the long arm of chromosome 3 (q26.3-27). Abnormalities in this gene occur in some hereditary forms of thrombocytosis (high platelet count) and in some cases of leukemia. The first 155 amino acids of the protein share homology with erythropoietin.[3]

Function and regulation

Thrombopoietin is produced in the liver by both parenchymal cells and sinusoidal endothelial cells, as well as in the kidney by proximal convoluted tubule cells. Small amounts are also made by striated muscle and bone marrow stromal cells.[1] In the liver, its production is augmented by interleukin 6 (IL-6).[1] However, the liver and the bone marrow stromal cells are the primary sites of thrombopoietin production.

Thrombopoietin regulates the differentiation of megakaryocytes and platelets, but studies on the removal of the thrombopoietin receptor show that its effects on hematopoiesis are more versatile.[1]

Its negative feedback is different from that of most hormones in endocrinology: The effector regulates the hormone directly. Thrombopoietin is bound to the surface of platelets by the mpl receptor (CD 110) and destroyed, thereby reducing megakaryocyte exposure to the hormone.[1] Therefore, the rising and dropping platelet concentrations regulate the thrombopoietin levels. Low platelets lead a higher degree of thrombopoietin exposure to the undifferentiated bone marrow cells, leading to differentiation into megakaryocytes and further maturation of these cells. On the other hand, high platelet concentrations lead to less availability of thrombopoietin to megakaryocytes.

Therapeutic use

Despite numerous trials, thrombopoietin has not been found to be useful therapeutically. Theoretical uses include the procurement of platelets for donation,[4] and recovery of platelet counts after myelosuppressive chemotherapy.[1]

Trials of a modified recombinant form, megakaryocyte growth and differentiation factor (MGDF), were stopped when healthy volunteers developed autoantibodies to endogenous thrombopoietin and then developed thrombocytopenia.[5] Romiplostim and Eltrombopag, structurally different compounds that stimulate the same pathway, are used instead.[6]

A quadrivalent peptide analogue is being investigated, as well as several small-molecule agents,[1] and several non-peptide ligands of c-Mpl, which act as thrombopoietin analogues.[7][8]

Discovery

Thrombopoietin was cloned by five independent teams in 1994. Before its identification, its function has been hypothesized for as much as 30 years as being linked to the cell surface receptor c-Mpl, and in older publications thrombopoietin is described as c-Mpl ligand (the agent that binds to the c-Mpl molecule). Thrombopoietin is one of the Class I hematopoietic cytokines.[1]

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Kaushansky K (2006). "Lineage-specific hematopoietic growth factors". N. Engl. J. Med. 354 (19): 2034–45. doi:10.1056/NEJMra052706. PMID 16687716.
  2. ↑ "Entrez Gene: THPO thrombopoietin (myeloproliferative leukemia virus oncogene ligand, megakaryocyte growth and development factor)".
  3. ↑ Online Mendelian Inheritance in Man (OMIM) 600044
  4. ↑ Kuter DJ, Goodnough LT, Romo J, et al. (2001). "Thrombopoietin therapy increases platelet yields in healthy platelet donors". Blood. 98 (5): 1339–45. doi:10.1182/blood.V98.5.1339. PMID 11520780.
  5. ↑ Li J, Yang C, Xia Y, Bertino A, Glaspy J, Roberts M, Kuter DJ (December 2001). "Thrombocytopenia caused by the development of antibodies to thrombopoietin". Blood. 98 (12): 3241–8. doi:10.1182/blood.V98.12.3241. PMID 11719360.
  6. ↑ Imbach P, Crowther M (August 2011). "Thrombopoietin-receptor agonists for primary immune thrombocytopenia". N. Engl. J. Med. 365 (8): 734–41. doi:10.1056/NEJMct1014202. PMID 21864167.
  7. ↑ Nakamura T, Miyakawa Y, Miyamura A, et al. (2006). "A novel nonpeptidyl human c-Mpl activator stimulates human megakaryopoiesis and thrombopoiesis". Blood. 107 (11): 4300–7. doi:10.1182/blood-2005-11-4433. PMID 16484588.
  8. ↑ Jenkins JM, Williams D, Deng Y, et al. (2007). "Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist". Blood. 109 (11): 4739–41. doi:10.1182/blood-2006-11-057968. PMID 17327409.

Further reading

External links

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