INT106483

Context Info Confidence 0.43 First Reported 2002 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 6 Total Number 14 Disease Relevance 5.87 Pain Relevance 0.27

plasma membrane (Mpl)

Anatomy Link Frequency astrocytes 7 platelet 6 megakaryocyte 4 brain 2 cerebellum 2 Mpl (Mus musculus)

Pain Link Frequency Relevance Heat cytokine 5 88.72 Hippocampus 81 85.44 Central nervous system 126 76.04 cerebral cortex 63 75.64 Angina 4 50.00 pruritus 2 30.40 imagery 9 26.60 palliative 2 26.40 Spinal cord 72 22.92 Thalamus 45 21.84

Disease Link Frequency Relevance Heat Erythremia 6 99.90 Myelodysplastic Syndromes 68 99.68 Thrombocytosis 4 99.08 Thrombosis 3 99.08 Myeloid Metaplasia 12 97.20 Erythrocytosis 37 96.24 Apoptosis 36 93.44 Neurodegenerative Disease 36 91.96 Fibrosis 5 89.44 Hypersensitivity 1 88.16

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Mpl protein expression seems to peak around birth (Figure 2D-K) , but is maintained in the adult murine brain (Figure 3; Table 1).

Negative_regulation (maintained) of Gene_expression (expression) of Mpl protein in brain

1) Confidence 0.43 Published 2010 Journal BMC Dev Biol Section Body Doc Link PMC2921376 Disease Relevance 0.07 Pain Relevance 0.04

The lack of Mpl expression in neuronal stem cells and the pattern of Mpl expression in the brain parenchyma support the concept that Thpo is critical for the selection of neurons to undergo apoptosis during a crucial period of neurogenesis.

Negative_regulation (lack) of Gene_expression (expression) of Mpl in parenchyma associated with neurodegenerative disease and apoptosis

2) Confidence 0.43 Published 2010 Journal BMC Dev Biol Section Body Doc Link PMC2921376 Disease Relevance 0.36 Pain Relevance 0.04

RT-PCR analysis of Mpl expression

Negative_regulation (analysis) of Gene_expression (expression) of Mpl

3) Confidence 0.43 Published 2010 Journal BMC Dev Biol Section Body Doc Link PMC2921376 Disease Relevance 0 Pain Relevance 0.04

Mpl and Thpo mRNA expression in primary neurons, astrocytes, microglia, and neuronal stem cells

Negative_regulation (microglia) of Gene_expression (expression) of Mpl in astrocytes

4) Confidence 0.43 Published 2010 Journal BMC Dev Biol Section Body Doc Link PMC2921376 Disease Relevance 0 Pain Relevance 0

However, in the adult cerebellum, Mpl expression was located in Purkinje cells (Figure 3J).

Negative_regulation (located) of Gene_expression (expression) of Mpl in cerebellum

5) Confidence 0.43 Published 2010 Journal BMC Dev Biol Section Body Doc Link PMC2921376 Disease Relevance 0 Pain Relevance 0.04

Amplification of Mpl transcripts showed the presence of Mpl expression not only in neurons, but also in cultured astrocytes (Figure 5A).

Negative_regulation (presence) of Gene_expression (expression) of Mpl in astrocytes

6) Confidence 0.43 Published 2010 Journal BMC Dev Biol Section Body Doc Link PMC2921376 Disease Relevance 0.05 Pain Relevance 0

Biochemical and molecular studies of PV patients have revealed no mutations in the Epo receptor, but granulocytes from PV patients have increased transcripts for the urokinase plasminogen activator receptor family member PRV-1 [8], whereas PV platelets show decreased expression of c-Mpl, the receptor for thrombopoietin [9].

Negative_regulation (decreased) of Gene_expression (expression) of c-Mpl in platelets associated with myelodysplastic syndromes

7) Confidence 0.28 Published 2006 Journal PLoS ONE Section Body Doc Link PMC1762384 Disease Relevance 1.64 Pain Relevance 0.03

Mpl and Thpo mRNA expression in primary neurons, astrocytes, microglia, and neuronal stem cells

Negative_regulation (microglia) of in neuronal stem cells Gene_expression (expression) of Mpl in astrocytes

8) Confidence 0.15 Published 2010 Journal BMC Dev Biol Section Body Doc Link PMC2921376 Disease Relevance 0 Pain Relevance 0

Mpl and Thpo mRNA expression in primary neurons, astrocytes, microglia, and neuronal stem cells

Negative_regulation (microglia) of in microglia Gene_expression (expression) of Mpl in astrocytes

9) Confidence 0.15 Published 2010 Journal BMC Dev Biol Section Body Doc Link PMC2921376 Disease Relevance 0 Pain Relevance 0

Mpl and Thpo mRNA expression in primary neurons, astrocytes, microglia, and neuronal stem cells

Negative_regulation (microglia) of in primary neurons Gene_expression (expression) of Mpl in astrocytes

10) Confidence 0.15 Published 2010 Journal BMC Dev Biol Section Body Doc Link PMC2921376 Disease Relevance 0 Pain Relevance 0

ET is defined by thrombocytosis and is distinguished from reactive states by decreased megakaryocyte c-Mpl expression, and a propensity for thrombosis.

Negative_regulation (decreased) of Gene_expression (expression) of c-Mpl in megakaryocyte associated with thrombocytosis, myelodysplastic syndromes and thrombosis

11) Confidence 0.06 Published 2002 Journal Int. J. Hematol. Section Abstract Doc Link 12430925 Disease Relevance 1.90 Pain Relevance 0.04

Polycythemia vera is distinguished from reactive erythrocytosis through erythropoietin independent growth of erythroid progenitors in vitro, suppressed levels of endogenous erythropoietin, possible overexpression of PRV-1 (polycythemia rubra vera-1), decreased c-Mpl expression on megakaryocytes, as well as overexpression of bcl-xL, and potentially aberrant activity of the Jak-Stat pathway.

Negative_regulation (decreased) of Gene_expression (expression) of c-Mpl in megakaryocytes associated with erythremia and erythrocytosis

12) Confidence 0.04 Published 2002 Journal Int. J. Hematol. Section Abstract Doc Link 12430925 Disease Relevance 1.71 Pain Relevance 0.04

We measured TPO and C-reactive protein (CRP), as well as monocyte-platelet binding and the platelet expression of P-selectin and of the TPO receptor, c-Mpl.

Negative_regulation (measured) of Gene_expression (expression) of c-Mpl in platelet

13) Confidence 0.02 Published 2006 Journal J. Am. Coll. Cardiol. Section Body Doc Link 17161245 Disease Relevance 0.08 Pain Relevance 0

The UA patients also showed reduced platelet expression of the TPO receptor, c-Mpl.

Negative_regulation (reduced) of Gene_expression (expression) of c-Mpl in platelet

14) Confidence 0.02 Published 2006 Journal J. Am. Coll. Cardiol. Section Body Doc Link 17161245 Disease Relevance 0.06 Pain Relevance 0

General Comments

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