Thrombopoietin

Source: Wikipedia, the free encyclopedia.
THPO
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl

ENSG00000090534

ENSMUSG00000022847

UniProt

P40225

P40226

RefSeq (mRNA)

NM_001173505
NM_009379
NM_001289894
NM_001289896

RefSeq (protein)

NP_001166976
NP_001276823
NP_001276825
NP_033405

Location (UCSC)Chr 3: 184.37 – 184.38 MbChr 16: 20.54 – 20.55 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

platelets.[5]

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.[6]

Genetics

The thrombopoietin

thrombocytosis (high platelet count) and in some cases of leukemia. The first 155 amino acids of the protein share homology with erythropoietin.[7]

Function and regulation

Thrombopoietin is produced in the liver by both parenchymal cells and

striated muscle and bone marrow stromal cells.[5] In the liver, its production is augmented by interleukin 6 (IL-6).[5]
However, the liver and the kidney are the primary sites of thrombopoietin production.

Thrombopoietin regulates the differentiation of

hematopoiesis are more versatile.[5]

Its negative feedback is different from that of most hormones in

CD 110). Inside the platelets it gets destroyed, while inside the megakaryocytes it gives the signal of their maturation and consecutively more platelet production. The bounding of the hormone at these cells thereby reduces further megakaryocyte exposure to the hormone.[5] Therefore, the rising and dropping platelet and megakaryocyte concentrations regulate the thrombopoietin levels. Low platelets and megakaryocytes 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 and megakaryocyte concentrations lead to more thrombopoetin destruction and thus less availability of thrombopoietin to bone marrow.

TPO, like EPO, plays a role in brain development. It promotes apoptosis of newly generated neurons, an effect counteracted by EPO and neurotrophins.[8]

Therapeutic use

Despite numerous trials, thrombopoietin has not been found to be useful therapeutically. Theoretical uses include the procurement of platelets for donation,[9] and recovery of platelet counts after myelosuppressive chemotherapy.[5]

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.[10] Romiplostim and Eltrombopag, structurally different compounds that stimulate the same pathway, are used instead.[11]

A quadrivalent peptide analogue is being investigated, as well as several small-molecule agents,[5] and several non-peptide ligands of c-Mpl, which act as thrombopoietin analogues.[12][13]

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.[5]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000090534 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022847 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^
    PMID 16687716
    .
  6. ^ "Entrez Gene: THPO thrombopoietin (myeloproliferative leukemia virus oncogene ligand, megakaryocyte growth and development factor)".
  7. ^ Online Mendelian Inheritance in Man (OMIM): 600044
  8. PMID 15642952
    .
  9. S2CID 12119556
    .
  10. PMID 11719360
    .
  11. PMID 21864167
    .
  12. PMID 16484588
    .
  13. PMID 17327409
    .

Further reading

External links
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